68 results on '"Huan Chen"'
Search Results
2. An LSC-based MRD assay to complement the traditional MFC method for prediction of AML relapse: a prospective study
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Si-Qi Li, Lan-Ping Xu, Yu Wang, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, Wei Han, Yu-Qian Sun, Chen-Hua Yan, Meng Lv, Fei-Fei Tang, Xiao-Dong Mo, Yan-Rong Liu, Kai-Yan Liu, Ying-Jun Chang, and Xiao-Jun Huang
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Leukemia, Myeloid, Acute ,Neoplasm, Residual ,Recurrence ,Immunology ,Humans ,Transplantation, Homologous ,Prospective Studies ,Cell Biology ,Hematology ,Neoplasm Recurrence, Local ,Flow Cytometry ,Prognosis ,Biochemistry - Abstract
Li et al delineate a novel technique for assessing measurable residual disease (MRD) by the assessment of isolated leukemia stem cells (LSCs). They report that assessment of MRD in LSCs provides a better prediction of outcome than standard multiparameter flow cytometry.
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- 2022
3. Real-World Study of the Use of Iguratimod to Treat Chronic/Refractory ITP
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Zhuo-Yu An, Ye-Jun Wu, Yun He, Xiaolu Zhu, Haixia Fu, Fengrong Wang, Xiao-Dong Mo, Yuanyuan Zhang, Wei Han, Huan Chen, Yao Chen, Chenhua Yan, Yu-Hong Chen, Tingting Han, Yingjun Chang, Xiangyu Zhao, Lanping Xu, Kaiyan Liu, Xiaojun Huang, and Xiaohui Zhang
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
4. Efficacy and Safety of MSCs Plus Basiliximab for the Treatment of Steroid-Resistant aGVHD after Haploidentical Stem Cell Transplantation: A Multicenter, Randomized, Open-Label Trial
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Hai-Xia Fu, Xueyan Sun, Yuanyuan Zhang, Tingting Han, Xiao-Dong Mo, Meng Lv, Fengrong Wang, Chenhua Yan, Yu Wang, Jun Kong, Yuqian Sun, Huan Chen, Yao Chen, Yu-Hong Chen, Ren Lin, Li Gao, Kaiyan Liu, Xiaohui Zhang, Xi Zhang, Qifa Liu, Xiaojun Huang, and Lanping Xu
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
5. Development and Validation of a Prognostic Model Based on Clinical Biomarkers for Heart Failure in Adult Patients Following Allogeneic Hematopoietic Stem Cell Transplantation
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Aobei Zhang, Haixia Fu, Yuanyuan Zhang, Kaiyan Liu, Yu Wang, Xiao-Dong Mo, Wei Han, Tingting Han, Huan Chen, Yao Chen, Yuqian Sun, Xiaojun Huang, and Xiaohui Zhang
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
6. Thrombopoietin Levels Predict the Response to Avatrombopag Treatment in Patients with Persistent Thrombocytopenia after Haploidentical Hematopoietic Stem Cell Transplantation
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Haixia Fu, Meng Lv, Yuanyuan Zhang, Tingting Han, Xiao-Dong Mo, Fengrong Wang, Chenhua Yan, Jun Kong, Yu Wang, Yuqian Sun, Wei Han, Huan Chen, Yao Chen, Yu-Hong Chen, Lanping Xu, Kaiyan Liu, Xiaojun Huang, and Xiaohui Zhang
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
7. Machine-Learning Based Early Warning System for Prediction for Disseminated Intravascular Coagulation after Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Multicenter Study
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Xiao-Dong Mo, Chen-Cong Wang, Yi-Fei Cheng, Tian-Xiao Han, Xiao-Lu Zhu, Lan-Ping Xu, Xiang-Yu Zhao, Huan Chen, Wei Han, Chen-Hua Yan, Xiao-Hui Zhang, Yan Su, Ying-Jun Chang, Kai-Yan Liu, Yao Chen, Ting-Ting Han, Yun He, Jing-Zhi Wang, Hai-Xia Fu, Ye-Jun Wu, Yuan-Yuan Zhang, Feng-Rong Wang, Xiao-Jun Huang, Zhuo-Yu An, Yu Wang, and Yu-Hong Chen
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Oncology ,Disseminated intravascular coagulation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Multicenter study ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Early warning system ,business - Abstract
Introduction Allogeneic haematopoietic stem cell transplantation (allo-HSCT) has been demonstrated to be the most effective therapy for various malignant as well as nonmalignant haematological diseases. The wide use of allo-HSCT has inevitably led to a variety of complications after transplantation, with bleeding complications such as disseminated intravascular coagulation (DIC). DIC accounts for a significant proportion of life-threatening bleeding cases occurring after allo-HSCT. However, information on markers for early identification remains limited, and no predictive tools for DIC after allo-HSCT are available. This research aimed to identify the risk factors for DIC after allo-HSCT and establish prediction models to predict the occurrence of DIC after allo-HSCT. Methods The definition of DIC was based on the International Society of Thrombosis and Hemostasis (ISTH) scoring system. Overall, 197 patients with DIC after allo-HSCT at Peking University People's Hospital and other 7 centers in China from January 2010 to June 2021 were retrospectively identified. Each patient was randomly matched to 3 controls based on the time of allo-HSCT (±3 months) and length of follow-up (±6 months). A lasso regression model was used for data dimension reduction, feature selection, and risk factor building. Multivariable logistic regression analysis was used to develop the prediction model. We incorporated the clinical risk factors, and this was presented with a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal and external validation was assessed. Various machine learning models were further used to perform machine learning modeling by attempting to complete the data sample classification task, including XGBClassifier, LogisticRegression, MLPClassifier, RandomForestClassifier, and AdaBoostClassifier. Results A total of 7280 patients received allo-HSCT from January 2010 to June 2021, and DIC occurred in 197 of these patients (incidence of 2.7%). The derivation cohort included 120 DIC patients received allo-HSCT and 360 patients received allo-HSCT from Peking University People's Hospital, and the validation cohort included the remaining 77 patients received allo-HSCT and 231 patients received allo-HSCT from the other 7 centers. The median time for DIC events was 99.0 (IQR, 46.8-220) days after allo-HSCT. The overall survival of patients with DIC was significantly reduced (P < 0.0001). By Lasso regression, the 10 variables with the highest importance were found to be prothrombin time activity (PTA), shock, C-reactive protein, internationalization normalized ratio, bacterial infection, oxygenation, fibrinogen, blood creatinine, white blood cell count, and acute respiratory distress syndrome (from highest to lowest). In the multivariate analysis, the independent risk factors for DIC included PTA, bacterial infection and shock (P Conclusions Risk factors for DIC after allo-HSCT were identified, and a nomogram model and various machine learning models were established to predict the occurrence of DIC after allo-HSCT. Combined, these can help recognize high-risk patients and provide timely treatment. In the future, we will further refine the prognostic model utilizing nationwide multicenter data and conduct prospective clinical trials to reduce the incidence of DIC after allo-HSCT and improve the prognosis. Disclosures No relevant conflicts of interest to declare.
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- 2021
8. Prevalence and Risk Factors of Antibodies to Class I and II Human Leukocyte Antigens in Haploidentical Allograft Candidates: A Prospective Study on 3805 Subjects
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Xiao-Hui Zhang, Lan-Ping Xu, Fei-Fei Tang, Yu Wang, Ying-Jun Chang, Chen-Hua Yan, Kai-Yan Liu, Huan Chen, Wei Han, Ning Ma, Yu-Qian Sun, Yan-Rong Liu, Xiao-Dong Mo, and Xiao-Jun Huang
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biology ,business.industry ,Immunology ,Cell Biology ,Hematology ,Human leukocyte antigen ,Biochemistry ,Class (biology) ,biology.protein ,Medicine ,Antibody ,business ,Prospective cohort study - Abstract
The aim of this study is to investigate the prevalence and risk factors of anti-human leukocyte antigen (HLA) antibodies in haploidentical candidates. This study was completed at Peking University People's Hospital, Beijing China. We performed a prospective analysis of patients with hematological diseases concerning the prevalence and risk factors of anti-HLA antibodies. Patients were enrolled between July 2015 - December 2019. Serum was collected for PRAs test within 1 month before haploidentical transplantation. The risk factors, such as age, sex, total transfusion, red blood cell (RBC) transfusion, platelet (PLT) transfusion, pregnancy, disease duration and diagnosis were collected. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors of anti-HLA antibodies. Six hundred and eighty (17.9%) patients were positive for panel reactive antibodies (PRA)-class I, 360 (9.5%) for class II, 768 (20.2%) class I or II, and 272 (7.1%) positive for class I and II both. Multivariate analysis indicated that female was related to higher risk of having PRAs for class I (P = 0.011), class I or II (P = 0.009), anti-HLA-A (P = 0.015), anti-HLA-DP (P = 0.048) and also for having higher mean fluorescence intensity (MFI) (2000 or more) of PRAs in class I (P = 0.020) and class I or II (P = 0.005). Compared to patients with myelodysplastic syndrome (MDS), patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), aplastic anemia (AA) had a lower incidence for PRAs in class I, class II, class I or II, class I and II, anti-HLA-A. anti-HLA-B, anti-HLA-C, anti-HLA-DQ, anti-HLA-DR, anti-HLA-DP (Table 1). Prior pregnancy was a risk factor for PRAs (P < 0.001), and no previous pregnancy group having lower MFI of PRAs in class I (P = 0.001) and class I or II (P = 0.004). PLT transfusion (more than 4 times) rleted with a higher prevalence of PRAs (P < 0.001), and also had a higher MFI of PRAs in class II (P < 0.001), class I and II (P < 0.001). Patients with RBC transfusion (more than 3 times) had a higher prevalence of PRAs in class I (P = 0.001), class II (P = 0.029), class I or II (P < 0.001), anti-HLA-A (P = 0.001), anti-HLA-B (P < 0.001), anti-HLA-C (P = 0.007), anti-HLA-DQ (P < 0.001) and anti-HLA-DR (P = 0.011). In addition, diseases duration (8 months or more) was also associated with higher MFI of PRAs in class I (P = 0.023) and class I or II (P = 0.004). Subgroup analysis showed that 11.7% of pediatric patients were positive for PRAs in class I; 19.2% of adults, 17.9% of elder patients; 12.4% of males; 26.1% of females; 21.0% of patients with AML; 10.5% of patients with acute lymphoblastic leukemia (ALL); 18.9% of patients with AA; 30.3% of patients with MDS; 16.6% of patients with other hematological diseases. The positive rate of class II PRAs in children was 4.3%; 11.1% for adults; 9.5% for elder patients; 5.5% for males; 15.4% for females; 11.4% for patients with AML; 5.2% for patients with ALL; 10.3% for patients with AA; 17.2% for patients with MDS; 6.6% of patients with other hematological diseases. Multivariate analysis showed that, in children, PLT transfusion and diagnosis were the two main risk factors of PRAs in class I and class II (P < 0.001, P = 0.017). In adults, diagnosis (P = 0.003), transfusion (P < 0.001) and pregnancy (P < 0.001) were the three main factors associated with PRAs in class I and transfusion (P < 0.001) and pregnancy (P < 0.001) were the two main factors associated with PRAs in class II. In males, PLT transfusion (P < 0.001) and diagnosis (P < 0.001) were the two main factors associated with PRAs in class I and class II. In ALL subgroup, gender (P = 0.026, P = 0.048), pregnancy (P < 0.001) and transfusion (P < 0.001) were the three main factors associated with PRAs in class I and II. In AA subgroup, gender (P = 0.004) and PLT transfusion (P < 0.001) were risk factors for class I PRAs, pregnancy (P = 0.008) and PLT transfusion (P = 0.003) were risk factors for class II PRAs. In elder patients, females, AML, MDS and other diseases subgroup, transfusion and pregnancy were the two main factors associated with PRAs in class I and class II. Our results indicated that female sex, diagnosis, pregnancy, transfusion, disease duration were independent risk factors of anti-HLA antibodies in haploidentical allograft candidates, which provided evidence for best haploidentical donor selection. The risk factors of anti-HLA antibodies were different among total patients and those of cases in different subgroups. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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- 2021
9. Tacrolimus Plus High-Dose Dexamethasone Versus High-Dose Dexamethasone Alone As First-Line Treatment for Adult Immune Thrombocytopenia: The Phase 2, Open Label, Randomized Trial (TARGET 020)
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Zhuo-Yu An, Ye-Jun Wu, Yun He, Xiao-Lu Zhu, Hong-Xia Shi, Chen-Cong Wang, Hao Jiang, Jin Lu, Qian Jiang, Qiu-Sha Huang, Hai-Xia Fu, Feng-Rong Wang, Xiao-Dong Mo, Yu Wang, Xiang-Yu Zhao, Yuan-Yuan Zhang, Wei Han, Huan Chen, Yao Chen, Chen-Hua Yan, Jing-Zhi Wang, Ting-Ting Han, Yu-Hong Chen, Yi-Fei Cheng, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, and Xiaohui Zhang
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Abstract
Introduction Immune thrombocytopenia (ITP) is an acquired, organ-specific, autoimmune disease and one of the most common bleeding disorders seriously endangering human health. Glucocorticoids and intravenous immunoglobulin are first-line treatments recommended by guidelines for patients with ITP. However, approximately 50%-85% of patients relapse during the first year of treatment. In addition, long-term use of glucocorticoids increases the risk for dose- and time-dependent glucocorticoid-related complications and serious side effects. Therefore, in-depth studies investigating new solutions for the first-line treatment of ITP are urgently needed. Tacrolimus is a calcineurin inhibitor, which forms a complex by binding to FK506-binding protein. It is currently widely used in the prevention of graft-versus-host disease for organ transplantation as well as for the treatment of autoimmune diseases. In addition to recent retrospective studies and case reports demonstrating its effectiveness in ITP, tacrolimus has been shown to improve anti-platelet antibody-mediated thrombocytopenia in mice, suggesting it may be a potential treatment for ITP. The aim of this study was to compare two first-line treatment options for ITP-a standard glucocorticoid-only regimen versus tacrolimus in combination with a standard glucocorticoid regimen-to determine which could help patients achieve stable platelet counts faster and experience a longer duration of remission. Methods This open-label, randomized, phase 2 trial, enrolled adult ITP patients from seven different tertiary medical centers in China. Elderly patients had confirmed, newly diagnosed, treatment-naive ITP, platelet counts 50×10 9/L without any additional ITP-modifying therapy at the 6-month follow-up. Key secondary endpoints included initial response by day 14 (OR, platelet count ≥30×10 9/L and at least 2-fold increase in baseline platelet count and absence of bleeding; and CR, platelet count ≥ 100×10 9/L), duration of response, bleeding scores, and adverse events (AEs). This trial was registered with ClinicalTrials.gov (NCT04747080). Results Total 140 patients newly diagnosed with ITP were randomly assigned to either the tacrolimus plus HD-DXM (n=72) or HD-DXM monotherapy (n=68) groups. At the 6-month follow-up, the proportion of patients exhibiting SR was significantly higher in the tacrolimus plus HD-DXM group than in the HD-DXM monotherapy group (65.3% vs 42.6%, p= 0.007). Of the 140 patients with ITP (males accounted for 48.6%), the mean age was 32.8 years, the mean platelet count was 16.7×10 9/L. The combination group exhibited a higher 14-day early remission rate than the monotherapy group (76.4% vs 55.9%, P=0.001). Significantly fewer treatment failures occurred in patients randomly assigned to the combination group(19.4% vs 38.2%, P=0.0014). During the follow-up period, fewer patients in the combination group experienced relapse than in the monotherapy group; the median time to relapse was 77 days (Tacrolimus+HD-DXM) vs 36 days (HD-DXM). The combination group exhibited a lower proportion of bleeding events and a lower bleeding score. The incidence of serious AEs, rescue therapy, and treatment side effects were similar between the two groups, and treatment was well tolerated by all patients, with no grade 4 AEs or treatment-related deaths reported. There was no statistically significant difference in the incidence of treatment-related AEs between the two groups. Conclusions Low-dose tacrolimus plus HD-DXM was an effective and safe treatment for ITP as first-line therapy and elicited a sustained prolonged response in adults. This therapy may be a new treatment option for adult patients with ITP. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: It includes information or discussion of off-label drug use of tacrilimus.
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- 2021
10. Superiority of Leukemic Stem Cell-Based Minimal Residual Disease Assay to Traditional Multiparameter Flow Cytometry-Based Method for Relapse Prediction in AML Patients: A Prospective Study with Randomized Training and Validation Sets
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Ying-Jun Chang, Huan Chen, Wei Han, Xiao-Hui Zhang, Xiao-Dong Mo, Feng-Rong Wang, Yu-Hong Chen, Fei-Fei Tang, Yu-Qian Sun, Meng Lyu, Lan-Ping Xu, Yu Wang, Xiao-Jun Huang, Chen-Hua Yan, Kai-Yan Liu, and Si-Qi Li
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Minimal residual disease ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Leukemic Stem Cell ,Multiparameter flow cytometry ,business ,Prospective cohort study - Abstract
Background: Minimal/measurable residual disease (MRD) determined by multiparameter flow cytometry (MFC) is an important variable for relapse prediction and treatment approach selection in patients with acute myeloid leukemia (AML). We aimed to investigate whether leukemia-stem cell (LSC)-based assay is superior to traditional MFC methods, including LAIP and D-F-N assays, for MRD evaluation in predicting clinical outcomes. Methods: In this cohort study, a total of 360 AML patients who received allogeneic stem cell transplantation (allo-SCT) between July 2018 and November 2019 were prospectively enrolled. The patients were randomized (1:1) and classified into a training set (n=180) and a validation set (n=180). Posttransplantation MRD were according to LSC based assay, mainly including a cocktail of CD7, CD11b, CD22, CD56, Tim-3, and CLL-1 on CD34 +CD38 - cells, and traditional assay determined by MFC, respectively. Findings: In the training set, patients were classified as LSC positive group (group A) and LSC negative group (group B) according to a cutoff value of CD34 +CD38 -cocktail + LSCs as 0.004%. Subjects in group A had a higher cumulative incidence of relapse (CIR, 42.7% vs. 2.6%, P Interpretation: Our data suggest the superiority of LSC-based MRD assays such as higher sensitivity, low false negativity, and longer time for MRD positivity to relapse to traditional MFC MRD methods for outcome prediction in AML patients received allograft. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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- 2021
11. Harnessing Extracellular Vesicles from Red Blood Cells for Targeted Delivery of Therapeutic Peptides and RNAs for Leukemia Treatment
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Yuqi Yang, Migara Kavishka Jayasinghe, Marco Pirisinu, Jiahai Shi, Minh T.N. Le, Boya Peng, and Huan Chen
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Leukemia ,Chemistry ,Immunology ,medicine ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Extracellular vesicles ,Cell biology - Abstract
Extracellular vesicles (EVs) are emerging as a new class of natural drug carriers with intrinsic ability to deliver bioactive cargo at high efficiency and low toxicity. However, clinical applications of EVs are limited by the production scale and the delivery specificity. We have recently established a new platform for purification and surface modification of EVs from red blood cells (RBCs) that are scalable and versatile for targeted delivery of small-molecule drugs and RNA therapeutics (Usman et al, Nat. Com. 2019 and Pham et al, J. Extracell. Vesicles 2021). Here, we describe a new development of the method for conjugation of RBC-EVs to obtain a higher targeting efficiency. We conjugate RBC-EVs, not only with peptides and nanobodies, but also with monoclonal antibodies, by coupling peptide conjugated EVs with streptavidin-bound biotinylated antibodies. Our data demonstrate that the conjugation is stable and does not affect the physicochemical characteristics of EVs. Conjugation of EVs with a cyclic peptide targeting CXCR4 or a monoclonal antibody targeting CD33 promotes specific binding and uptake of the conjugated EVs by leukemia cells expressing the corresponding receptors. We further use CXCR4-targeting RBC-EVs to specifically deliver the pro-apoptotic peptide KLA to CXCR4-expressing leukemia cells. Delivery of KLA using CXCR4-targeting EVs significantly suppresses leukemia burden and increases survival in a leukemia xenografted mouse model. Antibody-conjugated RBC-EVs are used to deliver RNA antisense oligonucleotides to knockdown FLT3 and miR-125b in cell lines and in patient-derived xenograft models of leukemia. Finally, we demonstrate that peptide/antibody conjugated RBC-EVs are biocompatible and nonimmunogenic. Our study provides a new platform for targeted delivery of therapeutic peptides and RNAs that is highly efficient, stable, versatile and biocompatible for potential clinical applications in leukemia treatment. Migara Kavishka Jayasinghe, Marco Pirisinu, Huan Chen, and Yuqi Yang contributed equally to this work as first authors. Disclosures Jayasinghe: Carmine Therapeutics: Patents & Royalties. Shi: Carmine Therapeutics: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Le: Carmine Therapeutics: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.
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- 2021
12. Development and Validation of a Prognostic Model for Transplant-Associated Thrombotic Microangiopathy Following Allogeneic Hematopoietic Stem Cell Transplantation
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Xiao-Lu Zhu, Shan Chong, Xiao-Hui Zhang, Peng Zhao, Huan Chen, Xiao-Jun Huang, Wei Han, Xiao Liu, Yuan-Yuan Zhang, Ye-Jun Wu, Xiao-Dong Mo, Qingyuan Qu, Xiang-Yu Zhao, Yu-Hong Chen, Jing-Zhi Wang, Yu Wang, Chen-Hua Yan, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Wan Sun, Rui-Xin Deng, and Feng-Rong Wang
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Oncology ,medicine.medical_specialty ,Thrombotic microangiopathy ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Internal medicine ,medicine ,Prognostic model ,business - Abstract
Introduction Transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can result in multiorgan injury and increased risk for mortality. Renewed interest has emerged in the prognostication of TA-TMA with the development of novel diagnostic and management algorithms. Our previous study reported an adverse outcome in patients with TA-TMA and concomitant acute graft-versus-host disease (Eur J Haematol, 2018). However, information on markers for the early identification of severe cases remains limited. Therefore, this study is concentrated on the development and validation of a prognostic model for TA-TMA, which might facilitate risk stratification and contribute to individualized management. Methods Patients receiving allo-HSCT in Peking University People's Hospital with 1) a diagnosis of microangiopathic hemolytic anemia (MAHA) or 2) evidence of microangiopathy were retrospectively identified from 2010 to 2018. The diagnosis of TA-TMA was reviewed according to the Overall-TMA criteria (Transplantation, 2010). Patients without fulfillment of the diagnostic criteria or complicated with other causes of MAHA were excluded from analysis. Prognostic factors for TA-TMA were determined among patients receiving HSCT between 2010 and 2014 (derivation cohort). Candidate predictors (univariate P < 0.1) were included in the multivariate analysis using a backward stepwise logistic regression model. A risk score model was then established according to the regression coefficient of each independent prognostic factor. The performance of this predictive model was evaluated through internal validation (bootstrap method with 1000 repetitions) and external temporal validation performed on data from those who received HSCT between 2015 and 2018 (validation cohort). Results 5337 patients underwent allo-HSCT at Peking University Institute of Hematology from 2010 to 2018. A total of 1255 patients with a diagnosis of MAHA and/or evidence of microangiopathy were retrospectively identified, among whom 493 patients met the inclusion criteria for this analysis (269 in the derivation cohort and 224 in the validation cohort). The median age at the time of TA-TMA diagnosis was 28 (IQR: 17-41) years. The median duration from the time of transplantation to the diagnosis of TA-TMA was 63 (IQR: 38-121) days. The 6-month overall survival rate was 42.2% (208/493), and the 1-year overall survival rate was 45.0% (222/493). In the derivation cohort, patient age (≥35 years), anemia (hemoglobin 800 U/L) and elevated total bilirubin (TBIL >1.5*ULN) were identified by multivariate analysis as independent prognostic factors for the 6-month outcome of TA-TMA. A risk score model was constructed according to the regression coefficients (Table 1), and patients were stratified into a low-risk group (0-1 points), an intermediate-risk group (2-4 points) and a high-risk group (5-6 points). The Kaplan-Meier estimations of overall survival separated well between these risk groups (Figure 1). The prognostic model showed significant discriminatory capacity, with a cross-validated c-index of 0.770 (95%CI, 0.714-0.826) in the internal validation and 0.768 (95%CI, 0.707-0.829) in the external validation cohort. The calibration plots also indicated a good correlation between model-predicted and observed probabilities. Conclusions A prognostic model for TA-TMA incorporating several baseline laboratory factors was developed and evaluated, which demonstrated significant predictive capacity through internal and external validation. This predictive model might facilitate prognostication of TA-TMA and contribute to early identification of patients at higher risk for adverse outcomes. Further study may focus on whether these high-risk patients could benefit from early application of specific management. Disclosures No relevant conflicts of interest to declare.
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- 2020
13. Disease Risk Comorbidity Index for Patients Receiving Haploidentical Allogeneic Hematopoietic Transplantation
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Xiao-Hui Zhang, Chen-Hua Yan, Xiao-Dong Mo, Sining Liu, Xiao-Jun Huang, Kai-Yan Liu, Huan Chen, Wei Han, Yu Wang, Jing-Zhi Wang, Lan-Ping Xu, Feng-Rong Wang, and Yu-Hong Chen
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medicine.medical_specialty ,Scoring system ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Comorbidity ,Transplantation ,Internal medicine ,medicine ,Disease risk ,Multivariable model ,business ,Very high risk ,Comorbidity index - Abstract
Purpose or Background: We aimed to develop a disease risk comorbidity index (DRCI) based on Disease Risk Index (DRI) and Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) in patients receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Method or Case: We examined 889 patients undergoing haplo-HSCT from 2015 to 2016. We used a Cox multivariable model to identify factors prognostic of disease-free survival (DFS) in a training subset (n = 593). A weighted score using these factors was assigned to the remaining patients (validation cohort; n = 296). This work was supported by the Capital's Funds for Health Improvement and Research (grant number 2018-4-4089). Results or Progress: The multivariable model identified two independent predictors of DFS: DRI and HCT-CI before HSCT. A weighted score of 2 was assigned to very high risk DRI, and a weighted score of 1 was assigned to high-risk DRI and intermediate- and high-risk HCT-CI in the scoring system (i.e., haplo-HSCT). In the validation cohort, the 3-year DFS was 65.2% (95% CI, 58.2-72.2%), 55.8% (95% CI, 44.9-66.7%), and 32.0% (95% CI, 5.8-58.2%) for the low-, intermediate- and high-risk group, respectively (P=0.005). Haplo-DRCI can predict relapse (P Conclusion or Discussion: These data confirmed that haplo-DRCI can effectively risk stratifies haplo-HSCT recipients and provide the tool to better predict who will best benefit from haplo-HSCT. Disclosures No relevant conflicts of interest to declare.
- Published
- 2019
14. Risk Factors and Different Therapeutic Patterns of Late-Onset Hemorrhagic Cystitis after Haploidentical Allogeneic Stem Cell Transplantation
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Huan Chen, Wei Han, Xiang-Yu Zhao, Xiao-Dong Mo, Hai-Xia Fu, Yu-Hong Chen, Yu Wang, Yi-Fei Cheng, Xiao-Lu Zhu, Xiao-Jun Huang, Ying-Jun Chang, Jing-Zhi Wang, Kai-Yan Liu, Qiao-Zhu Zeng, Chen-Hua Yan, Xiao Liu, Yun He, Lan-Ping Xu, Ting-Ting Han, Xiao-Hui Zhang, Yao Chen, Fei-Fei Tang, and Yuan-Yuan Zhang
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Basiliximab ,business.industry ,medicine.medical_treatment ,Immunology ,Late onset ,Viremia ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Human leukocyte antigen ,medicine.disease ,Biochemistry ,Transplantation ,medicine ,Stem cell ,business ,medicine.drug ,Hemorrhagic cystitis - Abstract
Introduction Late-onset hemorrhagic cystitis (LOHC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with an incidence ranging from 6.5% to 70% and leads to prolonged hospitalization and even death (Silva Lde P et al, Haematologica, 2010; LAM et al, Transpl Infect Dis, 2017). The pathogenesis of LOHC remains obscure, but in our previous study, viral infections and acute graft-versus-host disease (aGVHD) have frequently been shown to be associated with its development (Han et al., Am. J. Hematol, 2014). Therapeutic strategies for LOHC are still not standardized due to the complicated clinical background and given the paradoxical phenomenon that immunosuppressive agents, such as steroids, are necessary for aGVHD but cause an immunosuppressive state. We aimed to investigate the incidence, risk factors and outcomes of LOHC after allogeneic stem cell transplantation. Additionally, for the first time, we propose four therapeutic patterns and their impact on prognosis of LOHC to aid in clinical decision making. Methods This retrospective, nested, case-control study reviewed data from 2158 patients who received allo-HSCT from January 2014 to December 2018. In total, 364 (16.87%) patients were diagnosed with LOHC. Individual matching was performed by randomly selecting 3 controls from the same cohort for each identified LOHC patient according to the time of allo-HSCT. Standard basic measures included hyperhydration, forced diuresis, insertion of a vesical catheter for intermittent or continuous bladder irrigation and evacuation of clots. Patients with grade III-IV LOHC were divided into four groups according to immunosuppressant use (steroid, MMF and Basiliximab) 1 week before and after the onset of LOHC: an intensified-intensified (I-I) group, intensified-not intensified (I-N) group, not intensified-intensified (N-I) group and not intensified-not intensified (N-N) group. "Intensified" was defined as an increase in any immunosuppressant, and "not intensified" was defined as maintenance or tapering of all immunosuppressants. Data concerning the baseline characteristics, incidence, treatment patterns and outcomes were recorded. Results In total, 364 patients developed LOHC at a median of 29 days (range, 23-37.75 days), with a cumulative incidence of 16.87%. AML (HR =0.493 95% CI, 0.244-0.997; p=0.049), AA (HR =0.444, 95% CI,0.18-1.096; p=0.078), HLA match(HR =0.149, 95% CI, 0.036-0.616; p=0.009), days to platelet engraftment(HR =1.023, 95% CI, 0.998-1.049;p=0.069)and CMV viremia (HR =2.365, 95% CI, 1.179,4.733;p=0.015)were associated with LOHC. Only HLA match (HR =0.111, 95% CI, 0.014-0.878; p=0.037)remained significant in the multivariate analysis. 6.5%, 12.9%, 48.39% and 32.26% patients with III-IV LOHC were divided into I-I, I-N, N-I and N-N groups, respectively. There were no significant differences in overall survival (p=0.05) and the incidence of CMV viremia (p=0.187) among the four groups. The incidence of relapse (p=0.007) and the incidence of aGVHD (p=0.01) was highest in the I-I group, followed by the N-I, I-N and N-N groups. 50% of the patients in N-I group showed the improvement of LOHC, which is significantly highest among the four groups(p=0.000). However, no statistical significance was found regarding the CMV viremia turning shade or the improvement of aGVHD. Non-relapse mortality (NRM) was observed in 25% of patients without resolution of LOHC. NRM was 0% among patients without intensified immunosuppression but was 25%, 0% and 50% among those with intensified immunosuppression before LOHC, after LOHC and before and after LOHC, respectively. Conclusion The independent risk factors for LOHC after allo-HSCT were HLA mismatch. Avoiding intensified immunosuppression that damages endothelium or reactivates the related virus may improve transplant outcome. The N-N pattern could reduce the incidence of CMV viremia or aGVHD in the LOHC patients, and the N-I pattern might be more promising as a therapeutic strategy for LOHC. Disclosures No relevant conflicts of interest to declare. Disclosures No relevant conflicts of interest to declare.
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- 2019
15. Haploidentical Hematopoietic Stem Cell Transplantation May Improve Prognosis in Non-Infant Children with t(v;11q23)/MLL-Rearranged B-Acute Lymphoblastic Leukemia
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Pan Suo, Huiren Chen, Yu Wang, Xiao-Jun Huang, Yu-Hong Chen, Chen-Hua Yan, Ai-Dong Lu, Yue-Ping Jia, Wei Han, Yi-Fei Cheng, Lan-Ping Xu, Xiang-feng Tang, Kai-Yan Liu, Jun Wu, Huan Chen, Jing-Bo Wang, Ying-Xi Zuo, Le-Ping Zhang, Yu-Qian Sun, and Lu Bai
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Lymphoblastic Leukemia ,Immunology ,Allopurinol ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,surgical procedures, operative ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Allogeneic hematopoietic stem cell transplant ,B Acute Lymphoblastic Leukemia ,business ,Burkitt's lymphoma ,Neoadjuvant therapy ,medicine.drug - Abstract
Background: B-acute lymphoblastic leukemia (B-ALL) with t(v;11q23)/MLL-rearrangement (MLL-r) in children (1 year or older) is rare, and its outcome and optimal treatment options remain controversial. This study aimed to analyze the clinical characteristics and outcomes of these patients, and to explore the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially haploidentical HSCT (haplo-HSCT) in the treatment of these patients. Methods: At the time of the last follow-up (July 1, 2019), we retrospectively analyzed clinical data of 42 non-infant children with t(v;11q23)/MLL-r B-ALL. Comparison of outcomes was made between patients received allo-HSCT in the first complete remission (CR1) and chemotherapy only. Results: The median follow-up was 41 (1-106) months. The median age at diagnosis was 4.5(1-14) years and the median leukocyte count was 56.0 (2.2-735.2)×109/L. One was excluded for death during induction. For the remaining 41 patients, the complete remission rate after induction therapy was 40/41 (97.6%), the estimated 4-year probabilities of overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 59.7%, 51.6% and 43.4%, respectively. 19 patients received allo-HSCT in CR1 (HSCT in CR1 cohort), notably, 18/19 cases in this cohort received haplo-HSCT, and the remaining 22 patients continued the consolidation therapy (Non-HSCT in CR1 cohort). The estimated 4-year probabilities of OS, EFS and CIR in the HSCT in CR1 cohort were 86.6%, 89.2% and 5.3%, respectively. Meanwhile, the estimated 4-year probabilities of OS, EFS and CIR in the Non-HSCT in CR1 cohort were 37.5%, 19.9% and 75.6%, respectively. They were considered to be statistically significant. Of the 17 patients who relapsed during consolidation chemotherapy, 9 patients who underwent chemotherapy only (Non-HSCT after relapse cohort) all died within 44 months. For the remaining 8 patients who chose allo-HSCT (HSCT in CR2 cohort) when they achieved the second complete remission (CR2), the estimated 4-year probability of OS was 47.6% (P=0.002). Multivariate analysis showed that HSCT in CR1 was the only independent protective factor for OS, EFS and CIR, and age at diagnosis (≥10 years) was an independent risk factor of OS. Conclusions: Allo-HSCT (especially haplo-HSCT) in CR1 may reduce the risk of relapse and improve prognosis in non-infant children with MLL-r B-ALL. In addition, allo-HSCT also seemed to be an effective approach to improve the prognosis of relapsed patients. Thus, haplo-HSCT could be an alternative approach for non-infant children with MLL-r B-ALL. Disclosures No relevant conflicts of interest to declare.
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- 2019
16. Rituximab for Desensitization during HLA-Mismatched Stem Cell Transplantation in Patients with a Positive Donor Specific Anti-HLA Antibody: A Prospective Study
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Chen-Hua Yan, Yu Wang, Huan Chen, Wei Han, Xiao-Jun Huang, Xiao-Hui Zhang, Ming-Rui Huo, Lan-Ping Xu, Yu-Hong Chen, Feng-Rong Wang, Xiao-Dong Mo, Kai-Yan Liu, Ying-Jun Chang, Yu-Qian Sun, Fei-Fei Tang, and Xiang-Yu Zhao
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business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Human leukocyte antigen ,Biochemistry ,Transplantation ,Medicine ,Rituximab ,In patient ,Stem cell ,business ,Prospective cohort study ,medicine.drug ,Desensitization (medicine) - Abstract
A prospective, clinical trial in non-manipulated haploidentical allografts was initiated to define the efficacy of a single dose of 375 mg/m2 rituximab as a desensitization regimen for donor-specific anti-HLA antibody (DSA)-positive patients with 2,000 ≤ mean fluorescence intensity (MFI) < 10,000. In the clinical cohort, compared to pretransplantation [median, 4791, n=28], the median MFI levels at day 7 [0], 14 [0], 21 [0], 30 [0], and 45 [0] following transplantation were significantly decreased (P This study is registered at http://www.chictr.org.cn/ChiCTR-OPC-15006672. Disclosures No relevant conflicts of interest to declare.
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- 2019
17. Who is the best donor for a related HLA haplotype-mismatched transplant?
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Xiao-Hui Zhang, Yao Chen, Xiao-Jun Huang, Ying-Jun Chang, Dan Li, Huan Chen, Feng-Rong Wang, Yu Wang, Chen-Hua Yan, Jing-Zhi Wang, Dai-Hong Liu, Kai-Yan Liu, Wei Han, Lan-Ping Xu, Yu-Hong Chen, and Ming-Rui Huo
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medicine.medical_specialty ,business.industry ,Donor selection ,Incidence (epidemiology) ,Immunology ,Hazard ratio ,Cell Biology ,Hematology ,Human leukocyte antigen ,Histocompatibility Testing ,Biochemistry ,Gastroenterology ,Confidence interval ,Internal medicine ,Medicine ,Sibling ,Young adult ,business - Abstract
The best donor for a related donor for a human leukocyte antigen (HLA) haplotype-mismatched transplant for hematological neoplasms is controversial. We studied outcomes in 1210 consecutive transplant recipients treated on a uniform protocol. Younger donors and male donors were associated with less nonrelapse mortality (NRM; hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.01-0.39; P = .008 and HR = 0.65; 95% CI = 0.49-0.85; P = .002) and better survival (HR = 0.73; 95% CI = 0.54-0.97; P = .033 and HR = 0.73; 95% CI = 0.59-0.91; P = .005). Father donors were associated with less NRM (HR = 0.65; 95% CI = 0.45-0.95; P = .02), acute graft-versus-host disease (GVHD) (HR = 0.69; 95% CI = 0.55-0.86; P = .001), and better survival (HR = 0.66; 95% CI = 0.50-0.87; P = .003) compared with mother donors. Children donors were associated with less acute GVHD than sibling donors (HR = 0.57; 95% CI = 0.31-0.91; P = .01). Older sister donors were inferior to father donors with regard to NRM (HR = 1.87; 95% CI = 1.10-3.20; P = .02) and survival (HR = 1.59; 95% CI = 1.05-2.40; P = .03). Noninherited maternal antigen-mismatched sibling donors were associated with the lowest incidence of acute GVHD compared with parental donors and noninherited paternal antigen-mismatched sibling donors. Specific HLA disparities were not significantly correlated with transplant outcomes. Our data indicate which HLA haplotype-mismatched related donors are associated with the best transplant outcomes in persons with hematological neoplasms.
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- 2014
18. Positive Stool Cultures Could Predict the Clinical Outcomes of Haploidentical Hematopoietic Stem Cell Transplantation
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Xiao-Dong Mo, Huan Chen, Qi Wang, Hui Wang, Chen-Hua Yan, Xiao-Jun Huang, Xiao-Hui Zhang, Yu Wang, Lan-Ping Xu, Yu-Hong Chen, Kai-Yan Liu, and Li-Juan Hu
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business.industry ,medicine.medical_treatment ,digestive, oral, and skin physiology ,Immunology ,Treatment outcome ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Stool specimen ,Biochemistry ,Neural stem cell ,Stool culture ,Medicine ,Platelet ,business - Abstract
We aimed to identify the impact of stool cultures on clinical outcomes among patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) (n=332). Positive stool cultures (PSC group) were observed in 61 patients (18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was associated with a higher risk of platelet engraftment failure. The cumulative incidence of non-relapse mortality at 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group; 22.2% vs. 12.7%, P=0.059). The probabilities of overall survival (71.4% vs. 83.8%, P=0.031) and disease-free survival (69.6% vs. 81.0%, P=0.048) at 1 year after haplo-HSCT were significantly lower for the PSC group than those of the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of non-relapse mortality and was associated with poorer survival. Our results showed that PSC impacted the clinical outcomes after haplo-HSCT, particularly for those who had Candida in their stool specimens. Disclosures No relevant conflicts of interest to declare.
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- 2018
19. Haplo-SCT Mediates Stronger GVL Effect Than HLA-Matched Sibling Allograft By Significantly Reducing Leukemia Burden
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Huan Chen, Xiao-Hui Zhang, Ying-Jun Chang, Chen-Hua Yan, Lan-Ping Xu, Xiao-Jun Huang, Kai-Yan Liu, and Yu Wang
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Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Minimal residual disease ,Transplantation ,Leukemia ,surgical procedures, operative ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Cumulative incidence ,business - Abstract
For AML patients with positive pre-transplant minimal residual disease (MRD), determined by multicolor flow cytometry (MFC), haploidentical stem cell transplantation (haplo-SCT) could achieve lower CIR rates than human leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT) (J Hematol Oncol. 2017;10(1):134).However, these data only provide indirect evidence supporting the idea that haplo-SCT might have a strong graft-versus-leukemia (GVL) effect compared with MSDT. Therefore, direct evidence is needed to determine whether treating AML with haplo-SCT has a stronger GVL effect. The real time-polymerase chain reaction (RT-PCR) has greater sensitivity and specificity than MFC for detecting leukemia-specific genes, such as RUNX1/RUNX1T1, and provides a better estimation of the leukemia burden. Based on the levels of RUNX1/RUNX1T1 transcripts determined by RT-PCR, our group found that treating high risk cases with t(8;21) AML, who did not achieve major molecular remission (MMR, defined as a >3-log reduction in RUNX1/RUNX1T1 transcripts), with allogeneic stem cell transplantation (allo-SCT) could reduce the CIR compared with chemotherapy alone (22.1% vs 78.9%, P < 0.0001). These findings suggest that allo-SCT is necessary for high-risk t(8;21) AML patients, which provides an opportunity to investigate whether haplo-SCT has a superior GVL effect compared with MSDT in treating AML. Therefore, we focused on t(8;21) AML cases with positive MRD pre-transplant who underwent allogeneic SCT. The purpose of this study was to investigate and provide direct evidence that a haploidentical allograft has superior anti-leukemia effects compared with a HLA-matched sibling allograft. In the present study, One hundred and thirty-five t(8;21) acute myeloid leukemia (AML) patients with positive pre-transplantation minimal residual disease who underwent a haplo-SCT or MSDT were enrolled in this study. The levels of RUNX1/RUNX1T1 transcripts were monitored and quantified by real-time quantitative PCR. The 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), leukemia-free survival (LFS), and overall survival (OS) were 19%, 21%, 60%, and 61%, respectively. The levels of RUNX1/RUNX1T1 were significantly lower in Haplo-SCT patients compared with MSDT patients at 60 (P=0.039) and 90 (P=0.004) days after transplant (Figure 1). Compared with pre-transplant, the leukemia burden in the haplo-SCT group was significantly more reduced than in the MSDT group at 30 (P=0.068), 60 (P=0.005), 90 (P Figure 1. Kinetics of log-transformed leukemia burden reduction (evaluated by RT-PCR for RUNX1/RUNX1T1) in all patients and subgroup cases who either received haplo-SCT or MSDT, using a repeated measures ANOVA. Disclosures No relevant conflicts of interest to declare.
- Published
- 2018
20. Hepatitis E Virus Infection after Haploidentical Hematopoietic Stem Cell Transplantation:Incidence and Clinical Course
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Huan Chen, Yu Wang, Yan-Di Xie, Wei Han, Hui Ma, Chen-Hua Yan, Haiying Zhang, Xiao-Jun Huang, Lan-Ping Xu, Fei-Fei Tang, Yu-Hong Chen, Xiao-Dong Mo, Ying-Jun Chang, Lai Wei, and Xiao-Hui Zhang
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Hepatitis ,biology ,business.industry ,viruses ,Incidence (epidemiology) ,medicine.medical_treatment ,Immunology ,virus diseases ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Hepatitis E ,medicine.disease ,medicine.disease_cause ,Biochemistry ,digestive system diseases ,Serology ,Hepatitis E virus ,Alanine transaminase ,Immunoglobulin M ,medicine ,biology.protein ,business - Abstract
Introduction: Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic hematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients treated with haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo-HSCT patients. Methods: From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo-HSCT at Peking University Institute of Haematology were screened for HEV infection using HEV serology. HEV RNA were performed when HEV-IgG and/or IgM antibodies were positive. Results: Acute HEV infection was identified in seven of these patients (3.9%), none of whom had developed a chronic HEV infection. The median time from haplo-HSCT to HEV infection was 17.5 (range, 6-55) months. Median peak alanine transaminase during HEV infection was 716 (range, 164-1763) U/L. In 7 cases, HEV infection was confirmed by the presentation of anti-HEV IgM + anti-HEV IgG (rising) (n=5) or HEV-RNA + anti-HEV IgM + anti-HEV IgG (n=2). None patients died of HEV infection directly. Two patients with HEV infection died showing signs of ongoing hepatitis and the median duration of HEV infection was 2.7 months. Five patients cleared HEV and the median duration of HEV infection was 1.5 (range, 1.0-5.7) months. Conclusions: In conclusion, HEV infection is a rare but serious complication after haplo-HSCT. We recommend screening of HEV infection in haplo-HSCT. Disclosures No relevant conflicts of interest to declare.
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- 2018
21. MXD1 Regulates the Imatinib Resistance of Chronic Myeloid Leukemiacells By Repressing BCR-ABL1 Expression
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Qiaoxia Zhang, Jin Lou, Xin Du, Yuming Pan, Na An, Heng Wang, Weihong Chen, and Huan Chen
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Myeloid ,Imatinib resistance ,Immunology ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Bcr abl1 ,Imatinib mesylate ,medicine.anatomical_structure ,Cell culture ,hemic and lymphatic diseases ,medicine ,Cancer research ,K562 cells - Abstract
Tyrosine kinase inhibitors have achieved unprecedented efficacy in the treatment of chronic myeloid leukemia (CML), however, imatinib resistance has emerged as a major problem in the clinic. Because the overexpression of BCR-ABL1 critically contributes to CML pathogenesis and drug resistance, targeting the regulation of BCR-ABL1 gene expression may be a novel therapeutic strategy. In this study, we found that the transcriptional repressor MXD1 showed low expression in CML patients and was negatively correlated with BCR-ABL1. Overexpression of MXD1 markedly inhibited the proliferation of K562 cells and sensitized the imatinib-resistant K562/G01 cell line to imatinib, with decreased BCR-ABL1 mRNA and protein. Further investigations using reporter gene analysis showed that MXD1 significantly inhibited the transcriptional activity of the BCR-ABL1 gene promoter. Taken together, these data show that MXD1 functions as a negative regulator of BCR-ABL1 expression and subsequently inhibits proliferation and sensitizes CML cells to imatinib treatment. Disclosures No relevant conflicts of interest to declare.
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- 2018
22. Occurrence and Severity of DLI Associated Chronic Gvhd Influence the Clinical Outcomes in Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation
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Xiao-Dong Mo, Xiao-Hui Zhang, Jing-Zhi Wang, Kai-Yan Liu, Wen-Jing Yu, Huan Chen, Yu Wang, Xiao-Jun Huang, Wei Han, Feng-Rong Wang, Chen-Hua Yan, Lan-Ping Xu, and Yu-Hong Chen
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Oncology ,medicine.medical_specialty ,Acute leukemia ,business.industry ,medicine.medical_treatment ,Immunology ,Complete remission ,Allopurinol ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Leukemia ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Chronic gvhd ,Allogeneic hematopoietic stem cell transplant ,business ,medicine.drug - Abstract
The aim of this study was to investigate the occurrence and severity of chemotherapy plus donor lymphocyte infusion (Chemo-DLI) associated chronic graft-versus-host disease (cGVHD) in a consecutive cohort of patients with acute leukemia who experienced relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT; n = 104). The 5-year cumulative incidence of complete remission (CR) after Chemo-DLI was 81.0% (95% CI, 73.3-88.7%) and 84.6% (95% CI, 74.5-94.7%) in the moderate and severe cGVHD groups, respectively, which was significantly higher than that of the mild cGVHD 40.9% (95% CI, 29.3-52.5%) and non-cGVHD groups 29.2% (95% CI 23.1-35.3%) (Figure 1). The cumulative incidence of non-relapse mortality was comparable between patients with and without cGVHD . The 5-year probabilities of progression-free survival after Chemo-DLI were 42.9% (95% CI, 26.2-70.2%) and 34.6% (95% CI, 15.3-78.2%) in moderate and severe cGVHD groups, respectively, which were both significantly higher than those of mild cGVHD 9.1% (95% CI, 2.4-34.1%) and non-cGVHD groups 8.3% (95% CI 3.3-21.3%) (Figure 2). The 5-year probabilities of overall survival after Chemo-DLI were 56.7% (95% CI, 38.9-82.7%) and 43.1% (95% CI, 22.1-84.0%), in moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD 9.1% (95% CI 1.8-47.1%) and non-cGVHD groups 14.9% (95% CI, 7.3-30.2%) (Figure 3). Our observations highlight the close relation between cGVHD and immune-mediated graft-versus-leukemia (GVL) effect in patients with relapse receiving Chemo-DLI; however, mild cGVHD may not be associated with a sufficiently strong GVL effect to induce remission and improve survival. Disclosures No relevant conflicts of interest to declare.
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- 2018
23. The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission
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Hao Jiang, Xiao-Hui Zhang, Bin Jiang, Dai-Hong Liu, Ying-Jun Chang, Yu-Hong Chen, Yu Wang, Hong-Hu Zhu, Wei Han, Lan-Ping Xu, Kai-Yan Liu, Huan Chen, Qian Jiang, and Xiao-Jun Huang
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Immunology ,Antineoplastic Agents ,Hematopoietic stem cell transplantation ,Biochemistry ,Gastroenterology ,Disease-Free Survival ,Young Adult ,HLA Antigens ,Recurrence ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Prospective Studies ,Prospective cohort study ,Chemotherapy ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Chemotherapy regimen ,Surgery ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,Treatment Outcome ,Cytogenetic Analysis ,Female ,business - Abstract
We report the results of a prospective, patient self-selected study evaluating whether haploidentical related donor stem cell transplantation (HRD-HSCT) is superior to chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia (AML) in first complete remission (CR1). Among totally 419 newly diagnosed AML patients, 132 patients with intermediate- and high-risk cytogenetics achieved CR1 and received chemotherapy alone (n = 74) or HSCT (n = 58) as postremission treatment. The cumulative incidence of relapse at 4 years was 37.5% ± 4.5%. Overall survival (OS) and disease-free survival (DFS) at 4 years were 64.5% ± 5.1% and 55.6% ± 5.0%, respectively. The cumulative incident of relapse for the HRD-HSCT group was significantly lower than that for the chemotherapy-alone group (12.0% ± 4.6% vs 57.8% ± 6.2%, respectively; P < .0001). HRD-HSCT resulted in superior survival compared with chemotherapy alone (4-year DFS, 73.1% ± 7.1% vs 44.2% ± 6.2%, respectively; P < .0001; 4-year OS, 77.5% ± 7.1% vs 54.7% ± 6.3%, respectively; P = .001). Multivariate analysis revealed postremission treatment (HRD-HSCT vs chemotherapy) and high WBC counts at diagnosis as independent risk factors affecting relapse, DFS, and OS. Our results suggest that HRD-HSCT is superior to chemotherapy alone as postremission treatment for AML.
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- 2012
24. Association Between C-Reactive Protein in the First 1-3 Days Post-Transplant and Allogeneic Immune Reactions in Pediatric Haploidentical Stem Cell Transplantation
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Chen, Yao, primary, Liu, Kai-Yan, additional, Huang, Xiao-Jun, additional, Huan, Chen, additional, Wang, Feng-Rong, additional, Wang, Jing-Zhi, additional, Zhang, Xiao-Hui, additional, Chen, Yu-Hong, additional, Wang, Yu, additional, Han, Wei, additional, Chen-Hua, Yan, additional, Zhang, Yuan-Yuan, additional, and Xu, Lan-Ping, additional
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- 2016
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25. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation
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Dao Pei Lu, Huan Chen, Mei-Jie Zhang, Chen Yh, Lan ping Xu, Kai Yan Liu, Lujia Dong, Yao Chen Zhang, Xiao-Jun Huang, Dan Li, Tong Wu, Han Yun Ren, Dai Hong Liu, Wei Han, and Zhi-Yong Gao
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Male ,Transplantation Conditioning ,Graft vs Host Disease ,Severity of Illness Index ,Biochemistry ,Gastroenterology ,Cohort Studies ,HLA Antigens ,Recurrence ,Antineoplastic Combined Chemotherapy Protocols ,Living Donors ,Treatment Failure ,Child ,Bone Marrow Transplantation ,Acute leukemia ,Leukemia ,Incidence ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.anatomical_structure ,Child, Preschool ,Histocompatibility ,Acute Disease ,Female ,Immunosuppressive Agents ,Adult ,medicine.medical_specialty ,Adolescent ,Immunology ,Internal medicine ,Severity of illness ,medicine ,Humans ,Transplantation, Homologous ,Busulfan ,Cyclophosphamide ,Antilymphocyte Serum ,Neoplasm Staging ,business.industry ,Infant, Newborn ,Infant ,Cell Biology ,medicine.disease ,Surgery ,Transplantation ,Relative risk ,Chronic Disease ,Bone marrow ,business - Abstract
The outcomes of 293 patients with leukemia undergoing HLA-identical sibling (n = 158) or related HLA-mismatched (n = 135) hematopoietic cell transplantation (HCT) performed during the same time period were compared. Patients received BUCY2 in HLA-identical sibling HCT or BUCY2 + ATG in mismatched HCT as conditioning regimens, followed by unmanipulated marrow and/or peripheral blood (PB) transplantation. All patients achieved full engraftment. The cumulative incidences of grades II to IV acute graft-versus-host disease (aGVHD) in the matched and mismatched cohorts were 32% (CI, 25%-39%) versus 40% (CI, 32%-48%, P = .13), respectively, with the relative risk (RR) = 0.64 (95% CI, 0.43-0.94), P = .02. The incidence of chronic GVHD did not differ significantly between the cohorts (P = .97). Two-year incidences of treatment-related mortality and relapse for matched versus mismatched were 14% (range, 9%-20%) versus 22% (range, 15%-29%) with P = .10 and 13% (range, 8%-19%) versus 18% (range, 10%-27%) with P = .40, respectively. Two-year adjusted leukemia-free survival (LFS) and overall survival were 71% (range, 63%-78%) versus 64% (range, 54%-73%) with P = .27 and 72% (range, 64%-79%) versus 71% (range, 62%-77%) with P = .72, respectively. Multivariate analyses showed that only advanced disease stage and a diagnosis of acute leukemia had increased risk of relapse, treatment failure, and overall mortality. In summary, HCT performed with related HLA-mismatched donors is a feasible approach with acceptable outcomes.
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- 2006
26. Identification and Validation of High-Risk Genes Contributing to Poor Prognosis in Multiple Myeloma Patients with chr1q Gain/Amplification
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Zhang, Shanshan, Cai, Linjing, Huan, Chen, Wang, Yuqi, Liu, Qifa, and Wei, Xiaolei
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The gain/amplification of 1q21 (1q gain/amp) is a common cytogenetic abnormality (CA) in multiple myeloma (MM) and implies poor outcome. Despite the dysregulation of numerous genes located in chromosome 1q due to gain/amplification, the pivotal genes influencing the prognosis of multiple myeloma remain undefined.
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- 2023
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27. CRIP1 Upregulated Along with chr1q-Gain Indicates Immune Dysregulation and Portends Poor Outcomes in Multiple Myeloma
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Zhang, Shanshan, Cai, Linjing, Hanzhen, Zhang, Wang, Yuqi, Huan, Chen, Wei, Xiaolei, and Liu, Qifa
- Abstract
Background:The gain of chromosome 1q (chr1q-gain), one of the frequently occurring copy number aberrations in multiple myeloma (MM), is associated with a poor prognosis. However, the specific high-risk genes involved and the underlying molecular mechanisms remain elusive.
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- 2023
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28. Haploidentical Stem Cell Transplantation for Rare Pediatric Diseases at Peking University People's Hospital
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Xiao-Jun Huang, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, Lan-Ping Xu, Kai-Yan Liu, Jing-Zhi Wang, Xiao-Hui Zhang, and Yao Chen
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Pediatrics ,medicine.medical_specialty ,business.industry ,Wiskott–Aldrich syndrome ,medicine.medical_treatment ,Immunology ,Leukodystrophy ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Disease ,medicine.disease ,Biochemistry ,Surgery ,Transplantation ,medicine.anatomical_structure ,Fanconi anemia ,medicine ,Bone marrow ,Stem cell ,business - Abstract
Background:Rare diseases requiring hematopoietic stem cell transplantation (SCT) present a challenge for BMT centers. The patients present at a low frequency, and there are often no established conditioning regimens for these disorders, especially for children without HLA matched sibling donors. We report the conditioning regimen using haploidentical related donors, and outcomes for the following rare disorders transplanted at our center from January 2013 through December 2015. During the past three years we had patients presented with the following: Fanconi anemia (FA), dyskeratosis congenital (DC), adrenal leukodystrophy (ALD) and Wiskott-Aldrich syndrome (WAS). Methods:We treated these children with rare disorders that required SCT at our center, and are reporting the transplant outcomes for these rare diseases. Results: All children were transplanted with haploidentical related donors using G-CSF mobilized bone marrow and peripheral blood stem cell. Conditioning regimens and treatment plans were mainly following Beijing protocol and varied with type of disease. Patient characteristics and outcomes are presented in Table 1. No graft failure occurred and three of 5 patients (60%) are alive and well with no evidence of disease. Conclusions: Our program has treated a variety of rare disorders with an event-free-survival rate of 60%. Our data suggests haploidentical SCT for rare pediatric diseases seems to be challenging and promising. Disclosures No relevant conflicts of interest to declare.
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- 2016
29. Optimal Dose of Antithymocyte Globulin in Conditioning Regimens for Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: Long-Term Outcomes of a Prospective Randomised Trial
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Yu-Hong Chen, Chen-Hua Yan, Xiao-Hui Zhang, Yao Chen, Huan Chen, Ying-Jun Chang, Feng-Rong Wang, Kai-Yan Liu, Jing-Zhi Wang, Yu Wang, Xiao-Jun Huang, Wei Han, Xiao-Dong Mo, and Lan-Ping Xu
- Subjects
medicine.medical_specialty ,Randomization ,Multivariate analysis ,Globulin ,biology ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Surgery ,Transplantation ,Haematopoiesis ,Graft-versus-host disease ,Internal medicine ,medicine ,biology.protein ,Cumulative incidence ,business - Abstract
Background: Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe GVHD in patients undergoing unmanipulated haploidentical stem cell transplantation (haplo-SCT). However, the optimal dose of ATG is unknown. Methods: In this open-label extension of a prospective, randomised trial, we compared the long-term outcomes of two ATG doses used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were randomly assigned (1:1) to 10 mg/kg (ATG-10) or 6 mg/kg (ATG-6) ATG. Patients and individuals assessing outcomes were masked to treatment allocation. Analysis of disease-free survival (DFS), GVHD-free/relapse-free survival (GRFS), relapse, non-relapse mortality (NRM), and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease-free patients who had survived for at least 6 months and had received regular follow-up evaluations. Results: Between December 2010 and May 2012, 224 patients were recruited. The median follow-up period was 1614 days (28-1929 days). The 5-year cumulative incidence was comparable between the ATG-6 and ATG-10 groups for relapse (12·8% vs. 13·4%, p=0·832) and NRM (11·6% vs. 17·0%, p=0·263). The 5-year probability of DFS was comparable between groups (75·6% vs. 69·6%, p=0·283). The 5-year cumulative incidence was higher with ATG-6 for cGVHD (75·0% vs. 56·3%, p=0·007; moderate-to-severe cGVHD: 56·3% vs. 30·4%, p Conclusions: ATG 10 mg/kg may be the optimal dose for conditioning regimens before unmanipulated haplo-SCT. Disclosures No relevant conflicts of interest to declare.
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- 2016
30. Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: To Allogeneic Stem Cell Transplantation or Not? a Single Center Experience
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Huan Chen, Xiao-Hui Zhang, Ya-Zhen Qin, Jing Wang, Bin Jiang, Xiao-Jun Huang, Lan-Ping Xu, Qian Jiang, Kai-Yan Liu, Jin Lu, and Hao Jiang
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Single Center ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Prednisone ,hemic and lymphatic diseases ,Acute lymphocytic leukemia ,Internal medicine ,medicine ,Cumulative incidence ,Chemotherapy ,Philadelphia Chromosome Positive ,business.industry ,Imatinib ,Cell Biology ,Hematology ,medicine.disease ,Surgery ,Transplantation ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Objectives: Compare the outcomes of allogeneic stem cell transplantation (allo-HSCT) versus a combination of imatinib and chemotherapy in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Explore prognostic factors and indentify those who may enjoy long-term survival without the risk of allo-HSCT. Methods: Between May 2006 to November 2015, data of consecutive newly-diagnosed Ph+ALL patients Results: 122 Ph+ALL patients were included. 64 patients were male (52.5%). Median age was 36 years (range, 14-65 years). 2 patients (1.6%) died before response assessment, and 115 (95.8%) achieved CR. With a median followed-up period of 20 months (range, 1-98 months) in all patients and 28 months (range, 4-98 months) in 99 survivors, 65 patients (56.5%) underwent allo-HSCT and 50 (43.5%) received continuous imatinib with chemotherapy. Cumulative incidence of relapse (CIR), disease-free survival (DFS) and overall survival (OS) rates at 3 years were 17.3%, 79.0% and 81.5%, respectively. Multivariate analyses in the total CR patients showed that BCR-ABL reduction Conclusions Our data suggest that allo-HSCT is a viable option for all patients with Ph+ALL. It is superior to a combination of imatinib and chemotherapy, conferring significant survival advantages to intermediate- and high-risk patients. However, the outcomes of imatinib plus chemotherapy and allo-HSCT are equally good in low-risk patients. For such patients, allo-HSCT may be considered as a salvage potion if there is evidence of TKI(s) resistance so long as the MRD is carefully monitored. Outcomes between allogeneic stem cell transplantation versus a combination of imatinib and chemotherapy. Outcomes between allogeneic stem cell transplantation versus a combination of imatinib and chemotherapy. Disclosures No relevant conflicts of interest to declare.
- Published
- 2016
31. Lower Incidence of Acute Gvhd Is Associated with the Rapid Recovery of CD4+CD25+CD45RA+ Regulatory T Cells in Patients Who Received Haploidentical Allografts from NIMA-Mismatched Donors: A Retrospective (development) and Prospective (validation) Cohort-Based Study
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Xiao-Su Zhao, Xiao-Dong Mo, Ying-Jun Chang, Yu Wang, Huan Chen, Wei Han, Kai-Yan Liu, Xiao-Jun Huang, Xiang-Yu Zhao, Yuan Kong, Lan-Ping Xu, Feng-Rong Wang, and Yuan-Yuan Zhang
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Oncology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Immunology ,chemical and pharmacologic phenomena ,Retrospective cohort study ,Cell Biology ,Hematology ,Biochemistry ,Flow cytometry ,Immune system ,Antigen ,Internal medicine ,Medicine ,Cumulative incidence ,In patient ,IL-2 receptor ,business ,Prospective cohort study - Abstract
To investigate the effects of non-inherited maternal antigen (NIMA) on clinical outcomes and immune recovery, especially of regulatory T cells (Tregs), in patients who underwent unmanipulated haploidentical transplantation.A retrospective cohort (n=57) and a prospective cohort (n=88) were included. Reconstitution of immune subsets, including Tregs, was determined using multicolor flow cytometry. In the retrospective cohort, the cumulative incidence of grades II-IV acute GVHD in patients with NIMA-mismatched donors was significantly lower than that of cases with NIPA-mismatched donors (14.8% vs. 43.30%, P=0.018). Patients with higher percentages of CD4+CD25+CD45RA+ T cells (naive Tregs) within CD4+ T cells recovered on day 30 (≥1.55%) experienced a significantly lower incidence of grades II-IV acute GVHD than that of cases with lower percentages of naive Tregs ( Disclosures No relevant conflicts of interest to declare.
- Published
- 2016
32. ADAM28 Enhanced the Growth and Dissemination of AML and Identified a Subgroup of AML Patients with a High Risk of Relapse in a Prospective Clinical Study
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Jin Lu, Chen-Cong Wang, Jia-Min Zhang, Meng Lv, Hao Jiang, Qian Jiang, Wei Han, Xiao-Hui Zhang, Kai-Yan Liu, Lan-Ping Xu, Xiao-Jun Huang, Yu Wang, Xiao-Lu Zhu, Huan Chen, Feng-Rong Wang, and Qian-Ming Wang
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Oncology ,Chemotherapy ,medicine.medical_specialty ,biology ,Cell growth ,business.industry ,medicine.medical_treatment ,Xenotransplantation ,Immunology ,Cell Biology ,Hematology ,biology.organism_classification ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Metastasis ,Leukemia ,Internal medicine ,Lentivirus ,medicine ,Cumulative incidence ,business - Abstract
Introduction ADAM28, a member of the ADAM family of metalloproteinases, is over-expressed in several human tumors and is related to cell proliferation and metastasis. Our previous study has demonstrated that the expression level of ADAM28 is significantly elevated in patients with relapsed acute lymphoblastic leukemia, which was associated with poor prognosis. However, the impact of ADAM28 on relapse and the prognosis of patients with AML remains unclear. Aims: To investigate the effect of ADAM28 on the growth and dissemination of leukemia cells and to identify the prognostic significance of ADAM28 levels in patients with AML. Methods and results From 2012-2013, 189 de novo AML patients were prospectively enrolled in this study. The expression of ADAM28 in the leukemic cells of AML patients at diagnosis was significantly higher than that in the donor BM cells. No correlations were found between the expression level of ADAM28 and either FAB classification or cytogenetic risk groups. However, the expression levels of ADAM28 differed significantly between patients suffering a relapse and those remaining in CR. Furthermore, the ADAM28 levels in the cerebrospinal fluid (CSF) of patients with central nervous system leukemia (CNSL) were significantly higher than those in patients without CNSL. These data suggested that ADAM28 levels might be related to the incidence of relapse in patients with AML. We further investigated whether ADAM28 could impact the proliferation, migration and invasiveness of leukemic cells in vitro. Primary AML cells with high ADAM28 expression levels have better proliferation, migration and invasion capacities than those with low ADAM28 expression levels. Knocking out ADAM28with aCRISPR/Cas9 lentivirus significantly inhibited the proliferation, migration and invasion in leukemic cells. The increased expression of ADAM28 lead to more prolific IGFBP-3 degradation and IGF-IR phosphorylation, whereas the ADAM28 knock out cells resulted in significant down-regulation of IGFBP-3 degradation and IGF-IR phosphorylation in leukemic cells. In a xenotransplantation mice model, primary cells with elevated ADAM28 expression have improved engraftment ability in hematopoietic tissue and enhanced dissemination into nonhematopoietic tissue compared with primary cells with lower ADAM28 expression. Blocking ADAM28 expression in leukemic cells ameliorated AML growth and dissemination after xenotransplantation. We then analyzed the prognosis of the cohort of AML patients. Patients were divided into a high expression group and low expression group according to the ADAM28 expression cutoff value based on the status of relapse. The cumulative incidence of relapse (CIR) and overall survival (OS) after a 3-year follow-up were used to evaluate the prognosis. The CIR after 3 years was significantly higher in the ADAM28 high expression group (p Conclusion ADAM28 improved the proliferation, migration and invasion of leukemic cells in which the IGF pathway was involved. High expression of ADAM28 enhanced the growth and dissemination of AML in vivo. ADAM28 expression levels also identified a new subgroup at higher risk for relapse and poor prognosis in favorable-risk AML patients, and this subgroup of patients which were allocated to chemotherapy, might benefit more from HSCT. Combining the expression level of ADAM28 with the existing risk stratification standard may be a more precise and preferable approach in predicting therisk of relapse in AML patients. Disclosures No relevant conflicts of interest to declare.
- Published
- 2016
33. MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial
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Xiao-Jun Huang, Yu-Hong Chen, Hong-Hu Zhu, Li Bao, Hao Jiang, Xiao-Hui Zhang, Yu Wang, Li-Ru Wang, Dai-Hong Liu, Ya-Zhen Qin, Jin Lu, Kai-Yan Liu, Yue-Yun Lai, Qian Jiang, Jing-Zhi Wang, Bin Jiang, Jun-Yue Chai, Wei Han, Feng-Rong Wang, Yan-Rong Liu, Huan Chen, and Lan-Ping Xu
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Neoplasm, Residual ,Adolescent ,Chromosomes, Human, Pair 21 ,medicine.medical_treatment ,Immunology ,Hematopoietic stem cell transplantation ,Biochemistry ,Risk Assessment ,Translocation, Genetic ,Young Adult ,hemic and lymphatic diseases ,Internal medicine ,Multicenter trial ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cumulative incidence ,Survival analysis ,Chemotherapy ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Consolidation Chemotherapy ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Minimal residual disease ,Combined Modality Therapy ,Survival Analysis ,Surgery ,Leukemia ,Leukemia, Myeloid, Acute ,Female ,business ,Chromosomes, Human, Pair 8 - Abstract
We aimed to improve the outcome of t(8;21) acute myeloid leukemia (AML) in the first complete remission (CR1) by applying risk-directed therapy based on minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels. Risk-directed therapy included recommending allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk patients and chemotherapy/autologous-HSCT (auto-HSCT) for low-risk patients. Among 116 eligible patients, MRD status after the second consolidation rather than induction or first consolidation could discriminate high-risk relapse patients (P = .001). Allo-HSCT could reduce relapse and improve survival compared with chemotherapy for high-risk patients (cumulative incidence of relapse [CIR]: 22.1% vs 78.9%, P < .0001; disease-free survival [DFS]: 61.7% vs 19.6%, P = .001), whereas chemotherapy/auto-HSCT achieved a low relapse rate (5.3%) and high DFS (94.7%) for low-risk patients. Multivariate analysis revealed that MRD status and treatment choice were independent prognostic factors for relapse, DFS, and OS. We concluded that MRD status after the second consolidation may be the best timing for treatment choice. MRD-directed risk stratification treatment may improve the outcome of t(8;21) AML in CR1. This trial was registered at http://www.chictr.org as #ChiCTR-OCH-12002406.
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- 2013
34. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation
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Xiao-Jun Huang, Chen-Hua Yan, Yan-Rong Liu, Lan-Ping Xu, Yu Wang, Huan Chen, Dai-Hong Liu, Wei Han, Ya-Zhen Qin, and Kai-Yan Liu
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Adult ,Male ,medicine.medical_specialty ,Neoplasm, Residual ,Adolescent ,Standard Risk Acute Leukemia ,medicine.medical_treatment ,Immunology ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Biochemistry ,Gastroenterology ,Donor lymphocyte infusion ,Young Adult ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Humans ,Transplantation, Homologous ,Child ,Acute leukemia ,Leukemia ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,Odds ratio ,Middle Aged ,medicine.disease ,Minimal residual disease ,Surgery ,Transplantation ,Graft-versus-host disease ,Treatment Outcome ,Child, Preschool ,Lymphocyte Transfusion ,Acute Disease ,Female ,business - Abstract
We studied the impact of risk stratification–directed interventions for minimal residual disease (MRD) on relapse and disease-free survival (DFS) prospectively in 814 subjects with standard-risk acute leukemia receiving allotransplantation in first or second complete remission. A total of 709 subjects were MRD− after transplantation (Group A); 105 subjects were MRD+, 49 received low-dose IL-2 (Group B), and 56 received modified donor lymphocyte infusion (DLI) with or without low-dose IL-2 (Group C). Posttransplantation immune suppression for GVHD was also modified based on MRD state. The cumulative risk of relapse was significantly less and DFS was significantly better in subjects in Group C than in subjects in Group B (P = .001 and P = .002, respectively), but was not different from subjects in Group A (P = .269 and P = .688, respectively). Multivariate analyses confirmed that MRD state and modified DLI were significantly correlated with relapse (P = .000, odds ratio [OR] = 0.255 and P = .000, OR = 0.269) and DFS (P = .001, OR = 0.511 and P = .006, OR = 0.436, respectively). These data suggest that risk stratification–directed interventions with modified DLI in patients with standard-risk acute leukemia who are MRD+ after transplantation may improve transplantation outcomes.
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- 2012
35. CTLA-4 Polymorphisms and Haplotype Correlate with Survival and aGVHD after Allogeneic Stem Cell Transplantation from Related HLA-Haplotype-Mismatched Donor
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Fengrong Wang, Jing-Zhi Wang, Ya-Zhen Qin, Ying-Jun Chang, Huan Chen, Kai-Yan Liu, Wei Han, Xiao-Hui Zhang, Xiao-Jun Huang, Lan-Ping Xu, Xiao-Ying Qin, Guo-Xuan Li, Zhengfan Jiang, and Yu Wang
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education.field_of_study ,Acute leukemia ,Donor selection ,medicine.medical_treatment ,T cell ,Immunology ,Haplotype ,Population ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biology ,Biochemistry ,Transplantation ,medicine.anatomical_structure ,medicine ,Cytotoxic T cell ,education - Abstract
Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure.T cell homeostasis is critical to determine the potency of the GVT effect. Cytotoxic T lymphocyte antigen-4 (CTLA-4 or CD152) is a T cell activation negative regulator. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT. Patients and Methods: In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 154 acute leukemia patients after related HLA-haplotype-mismatched transplantation. The four SNP genotypes (-1661, -318, CT60 and +49) were determined by TaqMan SNP genotyping assays. Results: Recipients of donors with +49 GG showed significantly lower OS (69.1% vs. 85.6%, P=0.024) and higher incidence of III-IV aGVHD (10.0% vs. 2.1%, P=0.032) than those with GA + AA(Fig.1,Fig.2). Multivariate analyses showed that +49GG was an independent risk factor for OS (HR:0.457,95%CI=0.227-0.920,P=0.028). Patients receiving mDLI showed significantly lower OS with +49 GG donor than those with AG+AA (P=0.011).The haplotype analysis revealed only three haplotypes in the donor population -1661/-318/CT60/+49 i.e.,ACGG,ACAA and GTGA,the frequencies were 64.3%, 19.5%, and 16.2%, respectively.Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcome as those with +49 GG and +49 AG+AA. Conclusion: The CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival and increased the aGVHD after allo-HSCT from the related HLA-haplotype-mismatched donor,knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy. CONFLICT OF INTEREST The authors declare no conflict of interest. Disclosures No relevant conflicts of interest to declare.
- Published
- 2015
36. Imatinib mesylate versus allogeneic hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in the accelerated phase
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Huan Chen, Yan-Rong Liu, Xiao-Hui Zhang, Bin Jiang, Ya-Zhen Qin, Lan-Ping Xu, Yue-Yun Lai, Xiao-Jun Huang, Yu Wang, Yu-Hong Chen, Dai-Hong Liu, Kai-Yan Liu, Wei Han, Qian Jiang, Hao Jiang, and Shan-Shan Chen
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,Antineoplastic Agents ,Leukemia, Myeloid, Accelerated Phase ,Hematopoietic stem cell transplantation ,Biochemistry ,Tyrosine-kinase inhibitor ,Disease-Free Survival ,Piperazines ,Cohort Studies ,Young Adult ,Risk Factors ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,neoplasms ,Hematology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Imatinib ,Cell Biology ,Middle Aged ,medicine.disease ,Surgery ,Transplantation ,Leukemia ,Imatinib mesylate ,Pyrimidines ,Treatment Outcome ,Benzamides ,Multivariate Analysis ,Imatinib Mesylate ,Female ,business ,Chronic myelogenous leukemia ,medicine.drug - Abstract
The relative merits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and imatinib for chronic myelogenous leukemia in the accelerated phase (AP-CML) have not previously been evaluated. This cohort study was designed to compare the outcomes of imatinib (n = 87) versus allo-HSCT (n = 45) for AP-CML. A multivariate analysis of the total population revealed that a CML duration ≥ 12 months, hemoglobin < 100 g/L, and peripheral blood blasts ≥ 5% were independent adverse prognostic factors for both overall survival (OS) and progression-free survival (PFS). Both treatments resulted in similar survival in low-risk (no factor) patients, with 6-year event-free survival (EFS), OS, and PFS rates of more than 80.0%. Intermediate-risk (any factor) patients showed no difference in EFS and OS, but 6-year PFS rates were 55.7% versus 92.9% (P = .047) with imatinib versus allo-HSCT, respectively. Among high-risk (at least 2 factors) patients, imatinib was by far inferior to allo-HSCT, with 5-year EFS, OS, and PFS rates of 9.3% versus 66.7% (P = .034), 17.7% versus 100% (P = .008), and 18.8% versus 100% (P = .006), respectively. We conclude that allo-HSCT confers significant survival advantages for high- and intermediate-risk patients with AP-CML compared with imatinib treatment; however, the outcomes of the 2 therapies are equally good in low-risk patients. All trials were registered with the Chinese Clinical Trial Registry (www.chictr.org) as CHiCTR-TNC-10000955.
- Published
- 2011
37. Comparative Survival of Haploidentical and Matched Related Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia
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Huan, Chen, primary, Liu, Kai-Yan, primary, Lan-ping, Xu, primary, Dai-hong, Liu, primary, Chen, Yu-hong, primary, Wei, Han, primary, Xiao-hui, Zhang, primary, Yu, Wang, primary, Ya-zhen, Qin, primary, Yan-rong, Liu, primary, and Huang, Xiao Jun, primary
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- 2014
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38. Reduced IL-35 Levels Are Associated with Increased Platelet Aggregation and Activation in Patients with Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
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Huan Chen, Shiyuan Zhou, Yi Zhou, Fei-Er Feng, Yu-Hong Chen, Wei Han, Xiao-Hui Zhang, Feng-Rong Wang, Qian-Ming Wang, and Xiao-Jun Huang
- Subjects
integumentary system ,business.industry ,medicine.medical_treatment ,Immunology ,Inflammation ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biochemistry ,Granulocyte colony-stimulating factor ,surgical procedures, operative ,medicine.anatomical_structure ,Cytokine ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Platelet ,Platelet activation ,Bone marrow ,medicine.symptom ,Progenitor cell ,business - Abstract
Introduction: Acute graft-versus-host disease (aGVHD) is a major limitation of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mechanism of aGVHD has not been completely elucidated. aGVHD is primarily caused by immune responses to allogeneic disparities between the donor and recipient organs (Nakamura K, et al. Bone marrow transplantation 2005). aGVHD can also lead to thrombotic complications through endothelial damage. Following endothelial injury, inflammation triggers platelet activation and leads to enhanced expression of CD62P, which can then interact with the P-selectin glycoprotein ligand 1 receptor expressed on monocytes and mediate the rolling of monocytes on activated endothelium, facilitating platelet-leukocyte aggregation and inducing platelet thrombus formation. IL-35 is a novel anti-inflammatory cytokine that suppresses the immune response. Previous work has demonstrated that IL-35 is an anti-inflammatory cytokine that suppresses the immune response through the expansion of regulatory T cells and suppression of Th17 cell development that has a protective function in various autoimmune disorders. In this study, we hypothesized that patients with aGVHD may have increased platelet aggregation, which is associated with an increased risk of thrombus formation in aGVHD. Because the increased platelet aggregation is caused by inflammation during aGVHD, and IL-35 is a novel anti-inflammatory cytokine, IL-35 could also inhibit platelet activation and aggregation in aGVHD patients. Methods: In this study, we prospectively studied a total of 65 patients who received allo-HSCT. We measured plasma levels of IL-35 inpatients just at the onset of aGVHD. We collected time-matched samples from patients without aGVHD to serve as controls after HSCT. We also detected the levels of IL-35 in granulocyte-colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) and G-CSF-primed bone marrow (GBM) to explore the relationship between IL-35 levels and the occurrence of aGVHD. Then, we analyzed platelet aggregation in patients with and without aGVHD. We also added IL-35 to the plasma of these patients to test its function on platelet aggregation and platelet activation. Results: The plasma levels of IL-35 were reduced in the patients with grade III-IV aGVHD (23.46 ng/ml) compared with the patients with grade I-II aGVHD (40.26 ng/ml, p Conclusions: The results imply that IL-35 may predict the occurrence of aGVHD, as well as inhibit platelet activation and aggregation. These data suggest that IL-35 might represent a potential effective therapeutic agent against aGVHD and prevent thrombotic complications after allo-HSCT. Disclosures No relevant conflicts of interest to declare.
- Published
- 2014
39. Desialylation Induces Apoptosis and Phagocytosis of Platelets in Patients with Prolonged Isolated Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation
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Chen-Cong Wang, Huan Chen, Fei-Er Feng, Xiao-Hui Zhang, Qian-Ming Wang, Lan-Ping Xu, Xiao-Jun Huang, and Wei Han
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medicine.diagnostic_test ,Phagocytosis ,Immunology ,Cell Biology ,Hematology ,Biology ,Sialidase ,Biochemistry ,Molecular biology ,Sialic acid ,Flow cytometry ,chemistry.chemical_compound ,chemistry ,Von Willebrand factor ,Apoptosis ,biology.protein ,medicine ,Platelet ,N-Acetylneuraminic acid - Abstract
Introduction: Prolonged isolated thrombocytopenia (PIT) represents a significant complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is associated with an adverse patient prognosis and higher transplant-related mortality owing to a higher risk of infection events, severe (grades 3 to 4) acute graft-versus-host disease (GVHD) and chronic GVHD. PIT is defined as a peripheral platelet count less than 100×109/L without sustained anemia or leukopenia for more than 3 months after allo-HSCT (Zhang X, et al. Biol Blood Marrow Transplant, 2011). However, the underlying mechanisms remain unclear. Different kinds of functional glycoproteins are expressed on the platelet surface, with sialic acid residues at the end of their glycan. Desialylation of platelet glycoproteins has been found to be associated with accelerated platelet clearance in refrigerated platelets (Gerard Jansen AJ, et al. Blood 2012). Platelet-specific glycoprotein GPIbα,the functional subunit of the von Willebrand factor receptor, was the majorly desialylated glycoprotein; NEU1, one of the four human sialidases, was the enzyme that catalyzed GPIbα desialylation. However, few studies have focused on this mechanism in patients suffering PIT after allo-HSCT. In this study, we hypothesized that desialylation on platelet surfaces is associated with PIT after allo-HSCT. The mechanisms participating in this process may include GPIbα clustering, platelet apoptosis and phagocytosis by macrophages. Patients and methods: Blood samples were collected 90 days after allo-HSCT from 70 patients with PIT. Samples from post-transplantation patients who have normal platelet counts were taken as controls. Sialylation and desialylation were measured by detecting specific lectins via flow cytometry. Human sialidase expression was determined by immunofluorescence, flow cytometry and reverse transcription PCR. Platelet apoptosis markers were measured by flow cytometry, and macrophages stimulated from THP-1 cells were used in the phagocytosis assay. Results: We tested sialic acid residues and the desialylation markers, including β-galactose and β-N-Acetyl glucosamine, on the platelet surface, and found that platelets from PIT patients had significantly higher desialylation levels. Serum sialic acid levels were measured, and the results showed higher levels in PIT patients. Further, NEU1 was found to be over-expressed on the surface of platelets from PIT patients, and was found to be the enzyme that catalyzed the platelet surface desialylation. To further reveal the mechanism that lead to PIT, we proved that GPIbα was the desialylated glycoprotein on platelets from PIT patients. We found that GPIbα desialylation and clustering in PIT patients induced changes in the expression of Bcl-2 family protein, as a 2-fold increase in active Bax expression and a similar decrease in Bcl-XL expression were observed. Depolarization of the inner mitochondria membrane was augmented in desialylated platelets from PIT patients, indicating increased platelet apoptosis. Moreover, macrophages stimulated from the THP-1 cell line preferred to phagocytose desialylated platelets from PIT patients in vitro; this process could be blocked by the sialidase inhibitor, DANA. In the in vitrostudy, we found that dexamethasone led to a 32% decrease in phagocytosis, whereas oseltamivir, an antiviral medicine that can block sialidase from influenza virus, could also partially function on human sialidase and protect 43% of platelets from phagocytosis. In conclusion, our results demonstrate that desialylation played a role in the mechanism of prolonged isolated thrombocytopenia after allo-HSCT, most likely through platelet apoptosis induction and increased phagocytosis by macrophages in the peripheral circulation. Dexamethasone and oseltamivir could decrease platelet apoptosis and inhibit platelet phagocytosis in vitro, implying a novel potential method for treating PIT after allo-HSCT. Disclosures No relevant conflicts of interest to declare.
- Published
- 2014
40. Prolonged Isolated Thrombocytopenia (PIT) Is Associated with Platelet Aggregation, Which Is Affected By Endothelial Progenitor Cells (EPCs) Following Allo-HSCT
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Huan Chen, Lan-Ping Xu, Wei Han, Shiyuan Zhou, Fei-Er Feng, Xiao-Jun Huang, and Xiao-Hui Zhang
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medicine.medical_specialty ,P-selectin ,business.industry ,medicine.medical_treatment ,Immunology ,CD34 ,Prostacyclin ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biochemistry ,Gastroenterology ,Transplantation ,Internal medicine ,medicine ,Platelet ,Platelet activation ,Progenitor cell ,business ,medicine.drug - Abstract
Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for malignant hematological diseases, but prolonged isolated thrombocytopenia (PIT) following allo-HSCT seriously decreases patient survival after transplantation. PIT was defined as a platelet count Methods and results We enrolled 78 patients who underwent allo-HSCT in our department due of various types of hematological malignancies, of which 38 patients were suffering from PIT and 40 were matched controls. In the patients suffering from PIT after allo-HSCT, a significantly higher percentage of BM EPCs percent were found compared with the control group (0.041%±0.022% v 0.021%±0.012%, p Then, we tested whether PGI2 levels had the same tendency as the EPCs. We found that in PIT patients, the serum PGI2 levels seemed to be higher than in the control group, but the difference did not reach statistical significance (379.23±43.41 pg/ml v 234.75±38.49 pg/ml, p=0.08). However, when classified into subgroups, serum PGI2 levels of patients with lower platelet counts were significantly higher than those of the controls (433.32±76.43 pg/ml v 234.75±38.49 pg/ml, p We also measured platelet aggregation and activation in the two groups. We found that platelet aggregation and activation (measured by CD62P and PAC-1, respectively) in PIT patients were significantly lower than in the control group (PLT aggregation: 21.2%± 5.5% v 29.2% ±8.7%, p Conclusion Patients suffering PIT after allo-HSCT have a higher percentage of BM EPCs, higher serum PGI2 levels and lower platelet activation and aggregation. These data might lead to new insight into the mechanism of PIT following allo-HSCT, and provide a potential avenue for treatment for PIT after allo-HSCT. Disclosures: No relevant conflicts of interest to declare.
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- 2014
41. Risk-Stratification Directed Prophylaxis with Additional Low-Dose of Methylprednisolone Can Reduce Acute Graft-Versus-Host Disease for Patients with Hematological Malignancies after Allogeneic SCT: A Randomized, Controlled, Clinical Trial
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Xiao-Dong Mo, Xiao-Jun Huang, Huan Chen, Fei-Fei Tang, Dai-Hong Liu, Yu-Hong Chen, Feng-Rong Wang, Ying-Jun Chang, Lan-Ping Xu, Yu Wang, Wei Han, Yu-Qian Sun, Kai-Yan Liu, Chen-Hua Yan, and Xiao-Hui Zhang
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medicine.medical_specialty ,Basiliximab ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Group A ,Gastroenterology ,Group B ,Surgery ,Transplantation ,Graft-versus-host disease ,Methylprednisolone ,Internal medicine ,medicine ,Cumulative incidence ,business ,medicine.drug - Abstract
The major complication of allogeneic HSCT-graft-versus-host disease (GVHD)-remains lethal and limits use of this important procedure, especially after unmanipulated haploidentical HSCT. Several studies have provided evidence that universal addition of corticosteroids for prophylaxis of GVHD can reduce the risk for acute GvHD grade II-IV in HLA-matched transplantation. However, corticosteroid, a non-specific immunosuppressive agent, may also contribute to high rates of infections. Our previous data suggest that the ratio of CD4/CD8 in allografts from haploidentical donors can stratify patients into high-risk and low-risk ones who will develop GVHD after transplantation. Recently, we indicated that low-dose of methylprednisolone (MP, 0.5 mg/kg/day) might be a well-tolerated, effective and inexpensive regimen in combination of MTX for therapy of GVHD, suggesting that low-dose corticosteroid may be used for the prophylaxis of GVHD without increasing infection. To investigate whether risk-stratification directed prophylaxis strategy can reduce the incidence of GVHD and improve survival in a hemogenous patient population who underwent unmanipulated haploidentical HSCT, we performed a prospective, randomized, controlled, clinical trial. A total of 228 patients were enrolled in this trial. All of the patients completed the study and were stratified as high-risk (n=145) and low-risk arms (n=83) according to the ratio of CD4/CD8 in allografts. Patients of the high-risk arms were randomly assigned in a 1:1 ratio to additional low-dose glucocorticoid prophylaxis group (Group A, n=72) and control group (GroupB, n=73). The groups were balanced with respect to patient and donor characteristics. Our results showed that the cumulative incidence of grade II-IV acute GVHD on day 100 was 20.9%±4.8% in Group A, which was comparable to Group C (25.5%±4.8%, P=0.430) and both of which were significantly lower than that of Group B (48.1%±5.9%, P<0.001). In addition, the onset time of grade II-IV acute GVHD was 25 (16-50) days, 15 (9-57) days, and 21 (10-58) days, respectively in Group A, Group B, and Group C (P<0.05, Group A vs. Group B or Group C). There were no significant difference in grade Ⅲ-IV acute GVHD among these three groups. The ratio of patients who developed glucocorticoid refactory acute GVHD and treated with basiliximab (anti-CD25 antibody) were 13.9% (10/72), 17.8% (13/73), and 22.9% (19/83), respectively, in Group A, Group B, and Group C, there is a trend that the incidence of basiliximab treated patients in Group C is higher than that of Group A (P=0.109). The median time for myeloid engraftment in Group A was 11 days (range: 10-21 days), which was significantly faster that those of Group B (13 days, range from 10 to 33 days, P<0.05) and Group C (13 days, range from 10 to 33 days, P<0.05). The median time for platelet engraftment in Group A was 12 days (range: 10-22 days), which was significantly faster that those of Group B (17 days, range from 6 to 255 days, P<0.01) and Group C (19 days, range from 8 to 260 days, P<0.01). In addition, risk-stratification directed prophylaxis with additional low-dose of MP did not increase the incidence of CMV, EBV reactivation, PTLD, relapse and TRM, as well as delay immune recovery after unmanipulated haploidentical HSCT. The 100 day cumulative incidence relapse and transplant-related mortality was not significantly different among patients in Group A, Group B, and Group C, respectively. The 100 day probabilities of LFS and OS were comparable among these three patient groups. In conclusion, we for the first time demonstrated that risk-stratification directed prophylaxis for GVHD with additional low-dose of MP could significantly decrease the incidence and delay the onset of grade II-IV acute GVHD without increasing infections and delaying immune recovery. Our data indicated that addition of glucocorticoid early after unmanipulated haploidentical transplantation could also accelerate hematopietic recovery [This study was registered at http://clinicaltrials.gov/ NCT01607580]. Disclosures No relevant conflicts of interest to declare.
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- 2014
42. Prolonged Thrombocytopenia Is Associated With Increases Of CD8+ CX3CR1+ Cells In The Bone Marrow After Allogeneic Hematopoietic Stem Cell Transplantation
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Yu-Hong Chen, Xiao-Jun Huang, Guo-Xiang Wang, Xiao-Hui Zhang, Hong-Hu Zhu, Feng-Rong Wang, Wei Han, Yan-Rong Liu, Kai-Yan Liu, Lan-Ping Xu, Huan Chen, and Dai-Hong Liu
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medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biology ,Biochemistry ,CXCR4 ,medicine.anatomical_structure ,Apoptosis ,hemic and lymphatic diseases ,medicine ,Bone marrow ,Complication ,Receptor ,CD8 ,Homing (hematopoietic) - Abstract
Prolonged thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation(allo-HSCT),which is associated with a high mortality and poor prognosis. The aim of this study was to assess the impact of the CD8+CX3CR1+ T cells on the development and maturation of megakaryocytes in patients with the prolonged thrombocytopenia after allo-HSCT in order to identify the risk factors related to thrombocytopenia after allo-HSCT. The changes in CD8+ T cells and their homing receptors CX3CR1, CXCR4 and VLA-4 in bone marrow of patients( N=89) with and without (N=94 ) prolonged thrombocytopenia following allo-HSCT and the impact of activated CD8+ T cells on apoptosis and ploidy of megakaryocytes in vitro ware determined. The percentage of CD8+CX3CR1+ T cells was significantly higher in prolonged thrombocytopenia patients than control (P Disclosures: No relevant conflicts of interest to declare.
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- 2013
43. Intracranial Hemorrhage and Mortality In 1461 Patients After Allogeneic Hematopoietic Stem Cell Transplantation For 6-Year Follow-Up: Study Of 44 Cases
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Huan Chen, Xiao-Hui Zhang, Kai-Yan Liu, Wei Han, Xiao-Jun Huang, Yu-Hong Chen, Lan-Ping Xu, and Dai-Hong Liu
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medicine.medical_specialty ,Subarachnoid hemorrhage ,Hematology ,business.industry ,medicine.medical_treatment ,Mortality rate ,Immunology ,Cell Biology ,Hematopoietic stem cell transplantation ,medicine.disease ,Fibrinogen ,Biochemistry ,Gastroenterology ,nervous system diseases ,Transplantation ,Hematoma ,Internal medicine ,medicine ,cardiovascular diseases ,business ,Complication ,medicine.drug - Abstract
Although cerebral complications and causes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were well documented, assessment of incidence rates and risk factors of intracranial hemorrhage (ICH) following allo-HSCT are less discussed. The clinical data of 1461 consecutive patients undergoing allo-HSCT in Peking University Institute of Hematology from January 2005 to June 2011 were retrospectively analyzed. Among these patients, 44 developed intracranial hemorrhage (ICH) and matched 176 patients control subjects were accrued. ICH was verified by computed tomography (CT) scan in all patients. Among the 1461 patients, 44 patients (3.0 %) developed ICH, including 29 patients (65.9%) with multiple location hemorrhage, 4 patients (9.1 %) with subdural hematoma (SDH), 8 patients (18.2%) with subarachnoid hemorrhage (SAH), and 3 patients (6.8%) with other hemorrhage in the brain parenchyma. The median time of appearance for ICH was 129 days (1-450). Survival after 6 year was significantly reduced in patients who developed ICH complications compared with control (47.1% vs. 75.7%,p Disclosures: No relevant conflicts of interest to declare.
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- 2013
44. KIT Mutation Versus MRD, Which Is More Important To Predict Relapse Of Acute Myeloid Leukemia With t (8; 21)?
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Li-Ru Wang, Qian Jiang, Hong-Hu Zhu, Hao Jiang, Yu Wang, Jun-Yue Chai, Huan Chen, Kai-Yan Liu, Dai-Hong Liu, Xiao-Jun Huang, Lan-Ping Xu, Jin Lu, Xiao-Hui Zhang, Ya-Zhen Qin, and Bin Jiang
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Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biochemistry ,Minimal residual disease ,Gastroenterology ,Transplantation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Cytarabine ,Cumulative incidence ,business ,Prospective cohort study ,medicine.drug - Abstract
Background Although acute myeloid leukemia (AML) with t (8; 21) translocation generally belongs to the favorable-risk AML subtypes, relapse occurs in about 40% of cases and long-term (>5years) survival less than 50%. KIT-mutation (KIT+) and minimal residual disease (MRD) levels have been demonstrated as two most important risk factors in several retrospective studies. Until now, only two prospective studies (Our AML05 trial; French CBF-2006 trial) have assessed their respective prognostic values (Zhu HH, et al. Blood 2013; 121:4056; Jourdan E, et al. Blood 2013; 121:2213). We found both KIT+ and MRD were independent risk factors for relapse, but Joundan et al found only MRD rather than KIT+ was sole prognostic factor for relapse in multivariate anaysis. Both studies did not perform a comprehensive subgroup analysis combining the two factors, and risk-adopt postremission treatment might also affect this assessment. Therefore, we performed a subgroup analysis combining KIT mutation and MRD in a prospective protocol AML05 to answer which is more important to predict outcomes of t(8;21)AML. Methods From July, 2005, to Jan, 2013, 114 patients with t (8; 21) AML after achieving complete remission were included in this analysis. KIT mutations in exons 17 and 8 were screened using the direct sequencing method. MRD was detected using quantitative PCR to detect the RUNX1/RUNX1T1 transcript. MRD-positive (MRD+) was defined as < 3 log reduction of RUNX1/RUNX1T1 transcript from baseline after second consolidation therapy. Sixty-two patients received high-dose cytarabine-based consolidation chemotherapy (CT) or autologous hematopoietic stem-cell transplantation (auto-HSCT), and 52 patients received allogeneic HSCT (allo-HSCT). Results When receiving CT/auto-HSCT as postremission treatment, KIT+ patients (n=19) had a higher 3 year cumulative incidence of relapse (CIR) than KIT-patients (n=43) (94.4% vs. 38.2%, p Conclusions Both KIT status and MRD level were important to predict relapse of t (8;21) AML. KIT+ patients hold a very high relapse risk. Disclosures: No relevant conflicts of interest to declare.
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- 2013
45. Effects Of Noninherited Maternal Antigen On The Occurrence Of Acute Graft-Versus Host Diseae After Unmanipulated Haploidentical Blood and Marrow Transplantation
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Feng-Rong Wang, Xiao-Jun Huang, Dai-Hong Liu, Wei Han, Lan-Ping Xu, Kai-Yan Liu, Huan Chen, Yao Chen, Jing-Zhi Wang, Yu Wang, Ming-Rui Huo, Chen-Hua Yan, Yu-Hong Chen, and Ying-Jun Chang
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medicine.medical_specialty ,Fetus ,Platelet Engraftment ,business.industry ,Incidence (epidemiology) ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Gastroenterology ,Transplantation ,Antigen ,Internal medicine ,medicine ,Cumulative incidence ,Sibling ,business ,Prospective cohort study - Abstract
Background Exposure to non-inherited maternal antigen (NIMA) in fetal and neonatal life has a lifelong immunological consequence. In haploidentical transplantation, the mismatched haplotype of the donor can originate from either the mother or the father. The aim of this prospective study is to investigate the effects of NIMA and non-inherited paternal antigen (NIPA) on transplant outcomes in patients who underwent unmanipulated haploidentical blood and marrow transplantation (HBMT). Methods Two hundred and eleven patients with hematological disease, including AML, ALL, CML, MDS, SAA, and others, who received haploidentical blood and marrow allgrafts were enrolled in this study. The stem cell source was G-CSF mobilized BM combined with PB. The conditioning regimen was modified BUCY plus ATG with 10mg/kg in total dosage. MTX, CSA, and MMF were used for prophylaxis of graft-versus-host disease. Results The median patient follow-up was 343 days (range, 7-573 days). The median time for neutrophil and platelet engraftment was 12 days (range 7-25 days) and 16 days (range 6-410 days), respectively. The cumulative incidence of grade 2-4 actue GVHD at day 100 after HBMT was 41.7%±3.8% The cumulative incidence of chronic GVHD at 1 year was 53.4%±4.1%. The 1-year probability of relapse, TRM, LFS, and OS at 1 year was 11.3%±2.3%, 8.3%±1.9%, 79.6%±3.0%, and 85.0%±2.8%, respectively. Among the 211 patients, multivariate analysis showed that high risk patients had a high relapse rate (HR: 3.699, 95%CI, 1.598-8.565, P=0.002) and low LFS (HR: 2.452, 95%CI, 1.322-4.546, P=0.004). Duration from diagnosis to transplantation (more than 6 months vs. less than or equal to 6 moths) was associated with a high incidence of TRM (HR: 3.175, 95%CI, 1.251-8.059, P=0.015). Young recipient age (HR: 0.969, 95%CI, 0.946-0.993, P=0.012) were associated with a low incidence of grade 2-4 actue GVHD. Multiple analysis also showed that patients who received allografts from NIMA mismatched donor and father donor had lower incidences of grade 2-4 actue GVHD compared to those of patients receiving allografts from mother (HR: 0.576, 95%CI, 0.334-0.996, P=0.048, and HR: 0.378, 95%CI, 0.126-1.137, 0.087, respectively). For subgroup patients who received allografts from sibling donors, multivariate analysis showed that sibling transplantations mismatched for NIMA had a significantly lower incidence of grade 2-4 acute GVHD than those with NIPA mismatched donors (HR: 0.257, 95%CI, 0.083-0.796, P=0.018). No effects of NIMA mismatch on relapse, TRM, LFS, and OS were found in the current study. Conclusions Our results suggest that HBMT from a NIMA mismatched donor can offer low indicence of grade 2-4 acute GVHD. In unmanipulated haploidentical settings, mother donor transplantation may be associated with high incidence of grade 2-4 acute GVHD. These data suggest a NIMA mismatched donor not a mother donor should be preffered as donor for unmanipulated haploidentical blood and marrow transplantation. Disclosures: No relevant conflicts of interest to declare.
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- 2013
46. Low WT1 Expression At Diagnosis Is a Strong Predictor On Poor Outcome In Patients With t(8;21) Acute Myeloid Leukemia
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Yan-Rong Liu, Hao Jiang, Qian Jiang, Huan Chen, Li-Ru Wang, Xiao-Hui Zhang, Xiao-Jun Huang, Lan-Ping Xu, Ya-Zhen Qin, Dai-Hong Liu, Jun-Yue Chai Mm, Yu Wang, and Hong-Hu Zhu
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medicine.medical_specialty ,Chemotherapy ,Receiver operating characteristic ,business.industry ,medicine.medical_treatment ,Immunology ,Hazard ratio ,Cell Biology ,Hematology ,Biochemistry ,Gastroenterology ,Minimal residual disease ,Chemotherapy regimen ,Surgery ,Transplantation ,Internal medicine ,medicine ,Cytarabine ,Cumulative incidence ,business ,medicine.drug - Abstract
Introduction Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. The dynamic patterns of AML1-ETO transcript levels during treatment and clinical outcome of patients vary greatly. Our AML05 trial revealed that minimal residual disease (MRD)status and treatment strategy were independent risk factors for outcome and that risk stratification treatment directed by MRD may improve the outcome of t(8;21) AML in CR1 (Blood 2013; 121:4056). As for pretreatment parameters, c-KIT mutation is a well-established adverse predictor on survival. However, a subset of t (8;21) AML patients without c-KIT mutation still showed poor clinical outcome. The prognostic value of WT1 transcript levels at diagnosis in AML has been investigated and the results were controversial. We wondered if WT1 expression associated with outcome in t (8;21) AML patients. Methods A total of 101 patients were included. They all were eligible cases who enrolled into AML05 trial from June 2005 to December 2012, and had available bone marrow samples at diagnosis. After 1 or 2 induction therapy and 2 cycles of intermediate-dose cytarabine-based consolidation therapy, fifty-seven patients continued cytarabine-based consolidation chemotherapy or received autologous-hematopoietic stem-cell transplantation (auto-SCT) and were defined as CT group, the remaining 44 patients received allogeneic SCT (allo-SCT) and defined as SCT group.WT1 and ABL transcript were tested by real time quantitative PCR, and WT1 transcript levels were calculated as WT1copies/ABL copies in percentage. The upper limit of normal bone marrows (NBMs) was 0.5%. c-KIT mutations in exon 8 and 17 were screened by direct sequencing. Results The median follow-up time was 25 (6-93) months for 73 alive patients. The cumulative incidence of relapse (CIR) at 3 years was 35.3%. The 3-year disease free survival (DFS) and overall survival (OS) rates were 57.2% and 62.8%, respectively. The median WT1 transcript levelsssof all patients were 9.1% (0.02%-99.3%). c-KIT mutation was detected in 31 patients. Receiver operating characteristics (ROC) curves revealed that WT1 transcript levels of 5.0% (1-log increase compared to the upper limit of NBM) were the best cutoff values to discriminate patients with different outcome. WT1 transcript levels of ≤5.0% were significantly associated with c-KIT mutation (23/42 vs 8/59, P0.05). In CT group, patients with WT1≤5% (n=19) had significantly higher CIR rate at 3-year, lower 3-year DFS and OS rate than those with WT1>5% (n=38), respectively (89.5% vs 27.9%, P5% and c-KIT mutation (+) (all P >0.05, Figure 1). Therefore, they were merged into one group (n=24). Thus, patients with WT1≤5% and/or KIT mutation (+) had significantly higher CIR rate at 3-year, lower 3-year DFS and OS rate than those with WT1>5% and c-KIT mutation (-) (n=33) in CT group, respectively (89.4% vs 27.4%,P5%) and treatment (chemotherapy/auto SCT vs allo-SCT) instead of other pretreatment parameters were independent prognostic factors for relapse (hazard ratio (HR) 0.20, 95% CI 0.093¨C0.44; 0.096, 95% CI 0.033¨C0.28. all P Conclusion Less than 1-log increase of WT1 transcript levels at diagnosis is a strong predictor on poor outcome in patients with t (8;21) AML, and allo-SCT could significantly improve outcome of such patients. Grant Support Bejing Municipal Science & Technology Commission(Z111107067311070) and Nature Science Foundation of China (81170483). Disclosures: No relevant conflicts of interest to declare.
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- 2013
47. Efficacy Analysis With Imatinib Monotherapy Was Superior To Allogeneic Hematopoietic Stem Transplantation In Pediatric Patients With Chronic Phase Of Chronic Myelogenous Leukemia
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Yan-Rong Liu, Yu-Hong Chen, Wei Han, Huan Chen, Qian Jiang, Lan-Ping Xu, Kai-Yan Liu, Dai-Hong Liu, Shan-Shan Chen, Xiao-Jun Huang, Hao Jiang, Bin Jiang, Xiao-Hui Zhang, Ya-Zhen Qin, and Yue-Yun Lai
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Body surface area ,Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Allopurinol ,Imatinib ,Retrospective cohort study ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Transplantation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,business ,Adverse effect ,Chronic myelogenous leukemia ,medicine.drug - Abstract
Introduction Whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) or imatinib should be first-line therapy for childhood chronic myelogenous leukemia in the chronic phrase (CML-CP) is controversial. This study compared imatinib monotherapy and allo-HSCT for the management of CML-CP in pediatric patients. Methods This was a retrospective study of children (aged Results 62 patients (40 males, 22 females) were enrolled: 41 received imatinib, and 21 received allo-HSCT. Median follow-up in the imatinib and allo-HSCT groups was 29 and 56 months, respectively. Imatinib was well tolerated. In the imatinib group, the cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) at 24 months were 96.6% (95%CI, 93.3–99.9%) and 85.6% (95%CI, 78.5–92.7%), respectively; patients achieved CCyR and MMR at a median of 3 and 6 months, respectively. In the allo-HSCT group, allografts were from an HLA-matched sibling (n=3), an HLA mismatched/haploidentical familial donor (n=15) or an unrelated donor (n=3). Twelve patients (57.1%) developed acute graft-versus-host disease (grades 2–6 in 7 patients), and 5 deaths were reported. 5-year OS in the imatinib and allo-HSCT groups was 97.1±2.9% and 73.7±10.3% (P=0.032), respectively, while 5-year EFS was 92.5±4.2% and 63.8±11.1% (P=0.041), respectively. Conclusion Treatment with imatinib yielded satisfactory cytogenetic and molecular responses, and superior 5-year OS and EFS to allo-HSCT. Disclosures: No relevant conflicts of interest to declare.
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- 2013
48. Risk-Stratification Treatment Directed by Minimal Residual Disease Improves the Outcome of Acute Myeloid Leukemia with t(8;21) in First Complete Remission: Results of the AML05 Multicentre Trial
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Hao Jiang, Hong-Hu Zhu, Qian Jiang, Jun-Yue Chai, Xiao-Jun Huang, Li-Ru Wang, Xiao-Hui Zhang, Ya-Zhen Qin, Huan Chen, and Dai-Hong Liu
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Hazard ratio ,Consolidation Chemotherapy ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biochemistry ,Chemotherapy regimen ,Minimal residual disease ,Surgery ,Transplantation ,Internal medicine ,Cytarabine ,Medicine ,Cumulative incidence ,business ,medicine.drug - Abstract
Abstract 139 Background Although patients with acute myeloid leukemia (AML) and the t(8;21) translocation generally have a favorable prognosis, relapse occurs in about 40% of cases and long-term (>5years) survival less than 50%. Patients with a KIT-mutation had an even higher relapse rate up to 70% and dismal survial. Once relapse, the outcome is extremely poor, even receiving allogeneic hematopoietic stem-cell transplantation (allo-HSCT).Therefore, rapidly identifying high-risk relapse patients and preemptively treating them with more aggressive therapy, such as HSCT, may decrease the chance of relapse and improve patient survival. We sought to improve outcome in patients with t(8;21) acute myeloid leukemia(AML) in first complete remission (CR) by applying risk-directed therapy that was based on measurements of minimal residual disease (MRD) by quantitative PCR during treatment. Methods From June 1,2005, to Dec 31, 2011, 137 patients with t(8;21) AML were enrolled at three centres. MRD was detected using quantitative PCR to detect the RUNX1/RUNX1T1 transcript. High-risk was defined by not achieving major molecular remission (MMR,> 3 log reduction of RUNX1/RUNX1T1 transcript from baseline) after second consolidation therapy or loss of MMR within 6 months since achieving MMR. Low-risk was defined by achieving MMR after second consolidation therapy and maintenance of MMR within 6 months thereafter. High-risk patients were recommended to receive allogeneic hematopoietic stem-cell transplantation (allo-HSCT) and low-risk patients to high-dose cytarabine-based consolidation chemotherapy. 116 patients who achieved CR and completed second consolidation were assigned to risk-directed therapy. Finally, sixty-nine patients actually received risk-directed therapy and 47 patients received a non risk-directed treatment for patients¡ bias. Findings With a median follow-time of 36 months in patients alive, risk-directed therapy and non risk-directed therapy achieved 5 year cumulative incidence of relapse(CIR) of 15.0%±4.7% and 57.5%±8.0%(p Interpretation Risk-stratification treatment directed by MRD could improve the outcome of AML with t(8;21) in first complete remission. Allo-HSCT benefits high-risk as well as KIT-mutated but impairs low-risk patients¡ survival. Disclosures: No relevant conflicts of interest to declare.
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- 2012
49. A Clinical Study On Rituximab for Probable and Proven EBV Disease Post Haematopoietic Stem-Cell Transplantation
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Ting Zhao, Yu-Hong Chen, Xiao-Hui Zhang, Feng-Rong Wang, Xiao-Jun Huang, Yu Wang, Yuan-Yuan Zhang, Chen-Hua Yan, Kai-Yan Liu, Wei Han, Chunli Zhang, Lan-Ping Xu, Dai-Hong Liu, Jing-Zhi Wang, and Huan Chen
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Incidence (epidemiology) ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Gastroenterology ,Surgery ,Transplantation ,Leukemia ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Rituximab ,Cumulative incidence ,Sarcoma ,Adverse effect ,business ,medicine.drug - Abstract
Abstract 4512 Objective: EBV disease manifest as EBV-associated tumors lymphoproliferative disease (PTLD) and probable EBV disease. It is a severe complication post haematopoietic stem-cell transplantation (HSCT) and may cause to death in very short time. We analyse the effect and safety of Rituximab for probable and proven EBV disease (PTLD) in HSCT recipients in our center retrospectively. Method: Diagnosis of EBV disease was based on the criteria described in guidelines from the Second European Conference on Infections in Leukemia. Between June 2006 and June 2012, 33 patients were diagnosed EBV disease and received Rituximab. 20 cases are Male, 13 cases female; the median age of the patients was 21 years (3–46 years). 18 cases with AML for HSCT, 10 cases with ALL, 1 case with MDS, 1case with CML, 2 cases with SAA, 1 case with Granulocytic sarcoma; 28 cases receive Haploidentical HSCT, 3 cases receive unrelated volunteer PBSCT,1 case received unrelated CBT,1 case received sibling matched donor HSCT for SAA. Conditioning regimen including modified BUCY/ATG or CY+ATG, GVHD prophylaxis include CSA/MTX/MMF. 11 cases diagnosed as PTLD with lymphanode pathology and 22 as probable EBV disease. one organ was involved in 13 cases, multiple organs involved in 20 cases. Patients received 3(1–6) infusions of 375 mg/m2 at one week interval. Results: There were no middle or severe side effects occur during Rituximab infusion. The overall response rate was 87.9%, the CR rate was 75.8%. The 1st, 2nd, 3rd,4th,8th week cumulative CR incidence from onset Rituxmab is 18.4±6.8%□A31.7±8.2%□A58.8±9.0%□A76.8±7.9%□A82.6+7.8% respectively. The cumulative incidence of CR is higer in single organ involved patients than in multiple organs involved patients, the 1st, 2nd, 3rd,8th week cumulative CR incidence from onset Rituxmab is 15.4±10.0% vs 10.0±6.7%□A69.2+12.8% vs 30.7+10.5%□A74.6+10% vs 52.0±11.5%, 100% vs 64.0±11.3% respectively, (p=0.015). The cumulative incidence of CR is higer in probable EBV disease group than that in documented PTLD group, the 1st, 2nd, 3rd,8th week cumulative CR incidence from onset Rituxmab is 13.6+7.3% vs 9.1+8.7%□A54.5+10.6% vs 29.3+14.3%□A77.3+8.9 % vs 39.4±15.4%, 87.9% ±7.4 vs 63.6±16.2% respectively, (p=0.050). Of 25 CR cases,19 patients are alive with no evidence of disease, all of 8 patients without CR died. The one-year and two-year projected survival is 76.8+7.7%% and 40.1+11.9% with a median follow-up 11.5(2.3–26) of months in surviving patients. The one-year and two-year projected survival from onset of Rituximab therapy is higher in single organ group than that in multiple organ group, it is 74.1±16.1% vs 45.7+11.8% and 74.1±16.1 vs 24.4±13.0% (p=0.015) respectively. The one-year and two-year projected survival from onset of Rituximab therapy is higher in probable EBV disease group than that in documented PTLD group, it is 85.2±8.0% vs 18.2±11.6% and 55.9±18.5 vs 18.2.4±11.6% (p=0.002) respectively. Conclusions: The use of rituximab appears to be a safe and relatively efficient therapy in EBV disease. The better response may get in early stage, that is one organ involved and probable EBV disease. So, we suggest Rituximab should gave based on probable EBV disease in early stage meanwhile Pathology was try to get as soon as possible. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2012
50. Imatinib Mesylate Is Superior to Allogeneic Hematopoietic Stem Cell Transplantation As the First-Line Therapy for Patients with Chronic Myeloid Leukemia in the Early Chronic Phase
- Author
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Xiang-Yu Zhao, Kai-Yan Liu, Hong-Xia Shi, Xiao-Dong Mo, Huan Chen, Xiao-Hui Zhang, Bin Jiang, Yan-Rong Liu, Ya-Zhen Qin, Yu-Hong Chen, Lan-Ping Xu, Yu Wang, Shan-Shan Chen, Yue-Yun Lai, Dai-Hong Liu, Hao Jiang, Qian Jiang, Meng Lv, Xiao-Jun Huang, and Wei Han
- Subjects
education.field_of_study ,medicine.medical_specialty ,Hematology ,business.industry ,medicine.medical_treatment ,Immunology ,Population ,Imatinib ,Cell Biology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Surgery ,Imatinib mesylate ,Quality of life ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,education ,business ,Prospective cohort study ,Chronic myelogenous leukemia ,medicine.drug - Abstract
Abstract 162 Background and Aims. The relative merits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) in the first chronic phase (CP) in the imatinib era have not previously been evaluated. This prospective cohort study was designed to compare the medical outcomes and quality of life (QOL), with imatinib versus allo-HSCT from an HLA-matched sibling donor for CML in the first CP including the early CP (ECP; a CML duration < 12 months) and the late CP (LCP; a CML duration ' 12 months). Patients and methods. From April 2001 to April 2010, patients treated consecutively at the Peking University People's Hospital, Peking University Institute of Hematology were nonrandomly assigned to treatment with imatinib or allo-HSCT according to whether the patient had an HLA-matched sibling donor; those with an HLA-identical sibling donor were assigned to the allo-HSCT group, and the others were assigned to the imatinib group. QOL of surviving patients still in the imatinib and allo-HSCT groups was measured by the Medical Outcomes Survey Short Form 36 (MOS SF-36) at the end of the study evaluation period in April 2011. Results. In total, 463 patients were recruited, 209 patients were assigned to the allo-HSCT group and 254 patients were assigned to the imatinib group, respectively.Based on a ten-year follow-up period, a multivariate analysis revealed that allo-HSCT was an independent adverse prognostic factor for event-free survival (EFS; estimated HR=2.4, P=0.002 and estimated HR=0.31, P Among the 392 surviving patients who were invited to participate in the QOL survey, 295 (75.3%) patients including 180 of 218 (82.6%) in the imatinib group and 115 of 174 (66.1%) in the allo-HSCT group, respectively, completed the questionnaires. A multivariate analysis revealed that there was no correlation between the treatment mode and the physical health for the total, ECP and LCP population, however, allo-HSCT was one of the independent factors associated with good mental health (estimated HR=0.5, P Conclusions. We concluded that imatinib confers significant survival advantages and a desirable QOL and is superior to allo-HSCT as the first-line therapy for patients with CML in the ECP. All trials were registered with www.chictr.org as CHiCHTR-TNC-10000955. Disclosure: No relevant conflicts of interest to declare. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2011
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